CRPS Primer

Written by CRPScontender with Edits and Contributions from u/ThePharmachinist
Published on December 15, 2023 Updated on March 7, 2024

Introduction: The CRPS Primer

Welcome to the CRPS Primer, an in-depth introduction to Complex Regional Pain Syndrome in plain English! This Primer includes twenty-two mini-articles that each have an explanatory section, some practical tips and tricks, and multiple referenced journal articles if you’re interested in taking a deeper dive into the source material or showing a particular paper to your healthcare provider or a loved one. Let’s get started!

The first thing to understand is that, while the most notable symptom of CRPS is usually the deep, burning, freezing, radiating pain, CRPS is actually at its core a dysfunction of the autonomic nervous system. While this usually starts and can remain as a localized autonomic dysfunction for many individuals, most often at the far end of a limb after an injury or surgery, because the nervous system is an interconnected network that controls our entire person, this condition can have multifaceted symptom presentation in multiple areas of the body that seem unrelated and the pain and dysfunction can spread from the original area, sometimes even becoming widespread, generalized, and/or systemic, which are often referred to as “full body” cases in the CRPS community. 

Before we explore CRPS itself, it’s important that we have a basic understanding of the structure of the nervous system and its functions. Our nervous systems are divided into several subgroups.^1,2 The first two largest divisions are the central nervous system (CNS) made of the brain and the spinal cord (also called the neuraxis) and the peripheral nervous system (PNS) made of all the nerves that branch off the spinal cord and go into the rest of the body. The PNS is further divided into sensory information coming into the brain and motor information going out from the brain. The motor subdivision gets divided again into somatic, which is voluntarily controlled and supplies motor impulses to skeletal muscles, and autonomic (ANS), which is involuntarily controlled and supplies motor impulses to visceral muscles, organs, and glands. 

Finally, the autonomic system is subdivided one more time into the “fight or flight” sympathetic nervous system (SNS) which works like the gas pedal, revving up the engine and burning through our fuel to either play or protect us from environmental or interpersonal threats, and the  “rest and digest” parasympathetic nervous system (PSNS), which works like the brakes, calming us down and bringing us to a state of relaxation, recovery, and connection or, alternatively, into hard override and disconnecting the sympathetic system from burning through our nervous system during a life threat when there is no viable way for us to get help, fight back, or escape. 

In CRPS, people experience a wide range of dysfunction in many of these subsystems: central and peripheral, sensory, motor, and autonomic, including both sympathetic and parasympathetic. Some individuals, due to the nature of their initial injurious event, length of CRPS, or other life factors, may also have dysfunction or damage to the larger somatic motor nerves that can be seen on EMG/NCS tests with symptoms that extend beyond the identified area of nerve injury; these tests typically come back as “normal” or “unremarkable” for the vast majority of those with CRPS.

Individuals with discrete nerve damage^3,4 are known as having CRPS-II, or what was previously called Causalgia, and these cases make up 15% or less of overall CRPS cases.^5,6,7 Everyone else without a discrete nerve injury in the peripheral nervous system fibers is diagnosed with CRPS-I, previously called Reflex Sympathetic Dystrophy (RSD), though they can have evidence of small fiber damage^8,9,10,11 via more extensive testing like a skin punch biopsy, laser evoked potentials (LEP), or quantitative sweat measurement system (Q-Sweat).¹² As the the diagnostic signs for CRPS-I and CRPS-II are identical, CRPS researchers are still determining if having these two separate categories is helpful or better overhauled.¹³

CRPS is a Sympathetically-Mediated Pain condition, particularly during early onset; this is why sympathetic nerve blocks are often recommended for the condition, to break the sympathetic input and disrupt the pain before it changes the structure of the central nervous system itself and becomes Sympathetically-Independent Pain, where it does not matter if the SNS is sending impulses or not because the brain has maladapted to the onslaught of pain signals; this transition from SMP to SIP usually happens somewhere between six and twelve months, so early, appropriate, and aggressive treatment is necessary for the best outcomes for the individual’s long-term health and well-being. 

Acute CRPS can go into full or partial remission if treated appropriately, but those with persistent cases usually have a poor prognosis that does not respond well to treatments and these individuals often live with considerable physical disability and cognitive impairments,^14,15 with a tendency to become more and more socially isolated with fewer and fewer resources as time goes on.^{16,17,18,19,20,21,22,23} 

This is not to say that those with persistent cases of longer than 12 months are without hope and should give up! That is not true! There are steps that can be taken to reduce our fear, increase our understanding, improve our care and quality of life, reclaim our autonomy and sense of self, integrate with a community that can relate with our lived experience and offer support, find resources, and bit by bit expand our world. We are not hopeless. We are not lost causes. It can seem like an impossible task to make informed choices in our own best interest when we don’t understand what is happening to us; that is what Primer hopes to take steps to address. 

Even those with Persistent CRPS of over a year will still likely notice that when they are stressed, afraid, angry, or ill—in other words, when their sympathetic nervous system is activated—their pain and dysfunction also increases; this is known as a flare, and these can last anywhere from a few hours to months, depending on the person and the particular situation they are experiencing and how quickly that sympathetic activation can be calmed down. This flaring is due to the sympathetically-driven pain portion of the condition. While during the SIP stage of the condition, pain and other symptoms are often present in daily life but hold fairly steady, primarily affected by weather, food, and activity; however, when flaring, pain, symptoms, and cognitive capacity can spike in irregular and unpredictable ways that are completely debilitating. 

Those who, when they aren’t flaring, are able to maintain some mobility or perhaps work a job, may become bed bound or need a wheelchair or be unable to do even simple tasks at work or the quality of their work may decrease significantly as their cognitive abilities go temporarily down the tubes as their brains are completely overwhelmed; some may even dissociate. The variable functionality of many individuals with CRPS is not an indication that they are lying about their capabilities or that they are making up or exaggerating their disabilities. 

One final note for this introduction, those with CRPS often deal with delegitimization of their health condition (also known as gaslighting) on the regular. They experience this from medical professionals, family members, friends, bosses, coworkers, and random people at the grocery store, the restaurant, in the parking lot. These experiences are psychologically damaging and call the individual’s character, pain, symptoms, lived experience, and connection to reality into question, undermining their mental competency and/or integrity. CRPS is often confused with or equated to either Psychosomatic/Conversion Disorder or Factitious/Malingering Disorder; both of these views are harmful, incorrect, and not supported by evidence.^{24,25,26,27,28} Promoting these unscientific views entrenches harmful stigmas about an already stigmatized and misunderstood condition that reduces our access to necessary and life-saving care; it is irresponsible and, in some cases, malicious to deny access to needed medical care and support for a condition with physical components by those without a clear and solid understanding of the underpinning mechanisms of Complex Regional Pain Syndrome on its various organizational levels.

CRPS does utilize the medial “suffering” pain tract and end in the limbic system, as opposed to using the lateral pain tract that ends in the cortex like many pains, which we will discuss in more detail in the Limbic section of this Primer, which means that the emotional and pain signals get intertwined (particularly the large, unpleasant emotions that cause the sympathetic nervous system to activate for self-protection), which create feedback loops that increase pain and dysfunction.²⁹ That does not mean the pain is psychosomatic in origin, that the person needs to simply attend mental health therapy and their disorder will disappear, that they are “dramatic,” “oversensitive,” that they are subconsciously “seeking attention” by creating a fake pain condition and playing it up and it “can’t really be that bad,” or that they are lying on purpose.  

While this Primer is not intended to be an advanced course on the molecular mechanisms or broader systemic effects of CRPS nor should it replace personalized healthcare with a trained medical professional who is CRPS-informed, it should be able to provide a solid foundational understanding for this condition.

It is my desire that this Primer will accomplish two main goals: 1) help those with CRPS and their loved ones make informed decisions in their own best interests, so they can improve their quality of life or help someone who has CRPS reclaim their autonomy, and 2) increase awareness for the broader public about what is happening internally for those with CRPS, so that the delegitimization and lack of understanding and uncompassionate behavior we experience in almost every vector of life is reduced, one person at a time. These articles are one to five pages each, so feel free to read whichever ones interest you, in whichever order you find suitable, at whatever pace you can manage. My deep compassion to you, and I hope you find these articles informative and assistive.

Budapest Criteria: How CRPS is Diagnosed

CRPS is diagnosed using a tool called the Budapest Criteria, which was created by the International Association for the Study of Pain in August 2003 in Budapest, Hungary.³⁰ This Criteria has now been in use for over 20 years.

The Budapest Criteria has a sensitivity of 0.85-0.99, which means that out of 100 people tested with this tool who actually have CRPS, it will be able to properly designate 85 to 99 people as having CRPS and there are few false negatives. It has a specificity ranging from 0.68-0.85, meaning that out of 100 people tested with this tool who do not have CRPS, the Criteria will be able to properly designate 68 to 85 people as not having CRPS, but will incorrectly give false positives for 15 to 32 people.^31,32

This is a much more accurate specificity rate than the 1993 Orlando Criteria, which is what the Budapest Criteria replaced after a decade, which had a specificity rate of only 0.41, giving false positives to almost 60% of those who received a diagnosis with that old Criteria who actually had a different condition.³³ Having a diagnostic tool with a better specificity rate was important, and the Orlando Criteria has been all but completely retired and the Budapest Criteria has taken its place due to its much more accurate ability to differentiate between those who do not actually have CRPS, so they can get treatment more appropriate to their needs.  

In 2019, a CRPS special interest group from the International Association for the Study of Pain met in Spain to address some ambiguities and issues in the Budapest Criteria before the ICD-11 went into effect on January 1, 2022; this came to be known as the Valencia Consensus.³⁴ While they covered several topics, some of the most important ones are:

• Reclassifying CRPS under “chronic primary pain”
• For CRPS-II, diagnostic signs must extend beyond the area of identified nerve injury
• Diagnostic signs of CRPS-I (without discrete nerve damage) and CRPS-II (with discrete nerve damage) are identical and the clinical relevance of these two subtypes remains unclear at the present
• Introduction of a third subtype that overlaps with either Type 1 or 2: CRPS with Remission of Some Features. This subgroup is for those who previously fully met CRPS diagnostic criteria, but now have a reduction of some signs and symptoms fall into this third formal category. Please note this does not indicate that the individual necessarily has an improved lived experience, reduced pain, nor are they usually free of all symptoms. At what point the ongoing condition becomes Resolved is an on-going topic that needs to be addressed in future research. 
• For spreading of CRPS, diagnostic criteria needs to be applied to each limb individually

CRPS is a diagnosis of exclusion, so providers need to make sure no other condition could better describe what the patient is experiencing and rule out differential diagnoses.  While there are several tests that can be used to support a CRPS diagnosis, there are no “gold standard” laboratory tests that will definitively reveal CRPS and it must currently be clinically diagnosed based on careful examination, the patient’s medical history, and the provider’s discretion, understanding of CRPS, and the Budapest Criteria.

Unfortunately for those with CRPS, getting a diagnosis often takes precious time, eating through the best opportunity to achieve remission while waiting for appointment availability, testing dates, and finding a competent doctor who is not only familiar with CRPS but also knows evidence-based ways to treat it. Remission is most likely to occur in the first six months after onset, and after twelve to twenty-four months, the likelihood of remission decreases significantly. Getting appropriate medical care in a timely manner is imperative for the long-term quality of life of these individuals. 

This is not to say that all hope is lost if you’re reading this after the six, twelve, or twenty-four month mark; it isn’t. However, you are in a different stage of life now, and it is important that you reframe your outlook for your future and re-evaluate your expectations of what recovery looks like for you now. 

Next, we’ll talk about what the Budapest Criteria is looking for, why that matters, what it’s telling you is going on inside your body, and practical ways you can help mitigate and reduce those symptoms to increase your quality of life and autonomy, so you can reclaim your sense of self that CRPS often strips from us.

If you are a caregiver, loved one, or medical provider, as we go through these next multiple sections, I ask you to remember that CRPS often strips us of purpose, meaning, and core aspects of our identity. You are likely reading this because you care and you want to help; that’s important and it matters. Thank you. Please, in your desire to help and enthusiasm to assist us “get better,” don’t crush our autonomy and take over our lives.  It can be hard to watch someone vibrant seem to fade away or burn out, and sometimes we want to push people to be who they were before. I ask you to consider that maybe who they were before is part of the reason they’re burning now, and them becoming that old version of themselves won’t help that person now. 

Encouragement is one thing; expectation is another. Dependability is one thing; dependence is another. Requests are different than demands. Coercion is not the same thing as compassion. Holding control at someone’s request for a specified time frame is different than claiming control over someone’s life without their enthusiastic consent. Emotional safety is the complete opposite of shutting down to protect yourself. 

A huge part of healthy living in CRPS is respecting our body’s boundaries, so that we do not cripple ourselves. This translates to relationships too: mutually respectful partnerships built on trust, safety, and consent. This can be challenging and uncomfortable, especially if our primary method of conflict resolution is fawning or freezing. But if we want to regulate our sympathetic nervous systems and manage our CRPS effectively, then it is necessary. We can do hard things. 

Let’s talk about it.

Sensory: Sensitivity and Burning

Where does that “I’m on fire” pain come from? And why are we so hypersensitive?

The first requirement of the Budapest Criteria is Sensory Dysfunction. This causes problems with proper nerve signaling in people with CRPS. We have several sizes of nerves; some control our motor functions, and some bring sensory information to the brain. In CRPS, the primary nerves that aren’t working properly are unmyelinated (no fatty “hyperdrive” sheath), very small C fibers and thinly myelinated, small A-delta fibers; both of these are sensory nerves that bring information to the brain.³⁵ 

A-delta fibers carry “fast” pain of a specific, sharp nature that stings; they respond to thermal (hot, cold) and mechanical (touch, pressure, vibration, sound) input. C fibers carry “slow” pain of a diffuse, dull nature that burns; they respond to thermal (hot, cold), mechanical (touch, pressure, vibration, sound), and chemical (monitors CO₂, O₂, pH levels, substance P, CGRP) input. C fibers account for about 70% of all pain-sensing nerves.³⁶ Sensory C fibers also control local, skin-level blood vessel dilation.^37,38

In CRPS, fluid accumulation applies pressure to the neurovascular bundle, causing spontaneous nerve firings from the small fibers.³⁹ There are also findings that indicate significant loss of both C fibers and A-delta fibers in CRPS-affected areas, even in those without signs of peripheral nerve damage.^40,41 

Hyperalgesia is an excessive pain response to a sensation that is usually minimally painful, such as a pinprick or a solid, friendly smack on the limb. Allodynia is a pain response to a sensation that is usually not painful, such as wearing clothes or wind blowing over your skin.

Now in CRPS, it’s a bit more complicated than just the small fibers being dysfunctional, and we’ll talk more about that closer to the end of this series, but I want to put this information we’ve just covered in a bit different wording. Small fibers that control motor functions are part of the sympathetic “fight or flight” nervous system;^42,43 this is the subsection responsible for self-protection and defensive behavior. This is extremely important to understand; if you take nothing else away from this entire series, please pay attention here. 

CRPS is a sympathetically-driven condition, even after it moves into the sympathetically-independent pain stage that restructures the central nervous system. The more active your sympathetic self-protection system is, the more flares you’ll have, the higher your pain will be, and the worse your symptoms will become. Effective treatment in CRPS starts with feeling and being safe, so that your sympathetic self-protection system can calm down and let your body begin to move into a parasympathetic healing state. 

Dr. Porges’ Polyvagal Theory is an excellent tool for any human, but especially those of us with CRPS.⁴⁴ It can help us understand where our nervous systems are and why and how to expand our window of tolerance,⁴⁵ so that we aren’t living in a state of toxic stress.⁴⁶ Particularly if we have experienced traumatic events in our lives, even if those events didn’t leave any physical scars behind, and especially if you experienced multiple Adverse Childhood Experiences,^47,48,49 knowing what it means to “flip your lid”⁵⁰ and how to move through the nervous system map and recognize each map section is so helpful in reclaiming agency over our emotions and our pain,⁵¹ which is driven relentlessly forward by our out of control sympathetic nervous systems. We’ll talk more about these concepts in the limbic section. 

The sympathetic nervous system is part of the autonomic nervous system, which works automatically and reflexively. It isn’t something we consciously control. Neuroception is the subconscious threat analysis we are constantly running to determine if we are in a safe environment or around safe people. We cannot trick ourselves into feeling safe when we really don’t nor can we command ourselves to “Feel safe NOW!” and miraculously get better; it doesn’t work like that. 

Some practical tips and tricks:

• Understand how the sympathetic nervous system plays a driving role in CRPS flares, emotional dysregulation, and symptom intensity. 
• Realize that feeling and being safe is extremely important in effective CRPS treatment. While it is a good idea to challenge yourself, ignoring your body’s boundaries, “punishing” yourself, or staying in environments or relationships that are harmful or dangerous will negatively impact your health. 
• Spontaneous small fiber firings can be caused by pressure on the nerves; reducing some of the fluid in the interstitial space can relieve some of this pressure and cause the nerve to fire less. We’ll talk more about this in the Vasomotor and Lymphatic sections. 
• Desensitization therapy is a common approach to treat allodynia and hyperalgesia in CRPS. Some PTs may recommend a CRPS patient stimulate their CRPS-affected area until they cry; I think this is not a neurobiologically sound approach and will not teach your body the lessons you are hoping to teach it. We want to positively reframe sensation to our body; while sensation may be unpleasant, it isn’t harming us. If we are pushing ourselves beyond our limits until we cry, we are activating our defensive, self-protection system and reinforcing that touch is painful and harmful. Punishment drives out pleasure and reward.⁵² If the goal of desensitization is to expand our world and reward tolerating uncomfortable sensation, this punishing, past-limits approach is not the way to go about it. 
• Some individuals have great success with Graded Motor Imagery or Mirror therapy.^53,54,55,56 These are inexpensive and non-invasive treatment options that address both sensory and motor aspects of CRPS. This approach requires deep visualization techniques, so if you have aphantasia, this approach may not be effective for you. However, if you have hypervizualization skills, you might have fantastic results.
• A new treatment option being researched is Virtual Reality to improve pain levels, body perception disturbances, and limb movement and daily function.^{57,58,59,60,61}
• The Masgutova Neurosensorimotor Reflex Integration MNRI Method is a gentle, non-invasive physical therapy that focuses on repairing and retraining damaged or dysfunctional autonomic reflex arcs, the base building blocks and foundation of all our higher and more complex functions.^{62,63,64,65,66} While having a MNRI-trained specialist at the beginning can be extremely helpful, once you know what to do, these are exercises that can be done anytime, anywhere with no special equipment. 
• Nerve glides are gentle stretches that focus on the peripheral nervous system that help prevent or reduce compression, irritation, entrapment, and increasing mobility of the nerves.
• Topical doxepin can provide analgesia for neuropathic pain and reduce the hypersensitivity of allodynia and hyperalgesia.^67,68,69
• Ketamine^{70,71,72,73,74,75,76,77,78,79,80} and lidocaine^81,82,83,84 are anesthetics that can be delivered via multiple routes of administration to relieve sensory pain. Intravenous infusions are often the most effective, particularly for those with widespread cases or involvement of multiple limbs, and can provide significant relief for several weeks to a few months. Ketamine also provides neuroplastic benefits and can provide even more long-term benefits, if one is able to take advantage of the plasticity to help retrain the nervous system over time.
• Some people have good results with spinal cord stimulators,^85,86 dorsal root ganglion stimulators,^87,88,89 or intrathecal pain pumps^{90,91,92,93,94} to provide pain relief and reduce dysfunctional nerve signaling, giving them increased quality of life and ability to do activities in which they otherwise would not have been able to participate. Others find that the leads on SCSs and DRGs migrate, making them less or ineffective, that they have a negative reaction to the materials in the leads, that it stops helping after several years, or (particularly for those who are quite thin) the battery is painful.
• Pulsed ElectroMagnetic Fields PEMF^{95,96,97,98,99,100,101} and repetitive Transcranial Magnetic Stimulation rTMS^102,103,104 are options to consider for reduced neuropathic pain, anti-inflammatory effects, and reduction of free radicals and oxidative stress damage.
• Understand Porges’ Polyvagal Theory: connection, calm, curiosity, compassion, groundedness, and Safety in the Social Engagement Orienting System of Ventral Vagal; concern, fear, anxiety, panic, irritation, anger, rage, and Mobilization for Danger in the Defensive Orienting System of Sympathetic; helplessness, dissociation, shame, hopelessness, trapped, prepared for death, and Immobilized for Life Threat in the Defensive Orienting System of Dorsal Vagal.¹⁰⁵ [This is a great image.]
• Hypoxia (insufficient oxygen supply to tissues) activates the dorsal vagal nervous system,¹⁰⁶ which as we will see in the next section can be a major problem for those with CRPS.
• Living with the relentless pain of CRPS can easily distort pain scales of those who live with the condition, creating difficulties for them when asked to rate their pain 1-10 at doctor’s offices (which happens regularly) where either they feel they are under-reporting their subjective experience to be taken seriously by medical staff or they report in way that feels internally aligned with their subjective experience that then gets dismissed or delegitimized by medical staff and impedes their access to treatment. The Stanford Comparative Pain Scale gives descriptions of what severity of sensations fall at which number, similarly painful experiences, how much of your un-dissociated mental space it takes up, and how much it interferes with your activities and ability to live independently. This scale can be extremely useful, particularly for those who are neurodivergent and may have interoception issues, literal thinking, and difficulties with interpersonal communication.
• If you’re seeking an initial diagnosis, a pain management specialist or a neurologist are the two types of doctors most likely to be familiar with CRPS and comfortable diagnosing it. You are also more likely than standard to find knowledgeable providers with at least a base understanding or familiarity with CRPS in orthopedics, rheumatology, physiatry, physical therapy, and anesthesiology, who are willing to diagnose or offer referrals to more educated peers in neurology or pain medicine.
• Continuing care for CRPS often requires an entire team of interdisciplinary providers, but is usually centered and led by a pain management specialist. Finding a pain management provider with prior CRPS experience, who understands the condition, and who is patient-centered will greatly improve both quality of care and quality of life.

Vasomotor: Skin Color and Temperature Changes

The second requirement in the Budapest Criteria is Vasomotor Dysfunction. This causes problems with blood vessels and circulation for people with CRPS. It can cause the skin in CRPS-affected areas to be significantly warmer or colder than the corresponding area on the opposite limb or a suitable alternative site or a healthy control in the case of bilateral, multi-limb, or generalized CRPS. These temperature differences should be obvious to the back of the hand of an individual without impaired temperature sensation or greater than 1C/1.8F.¹⁰⁷ These circulation issues can cause skin color changes, making a wide variety of palette options. 

These changes are thought to come about due to a cycle known as an ischemia-reperfusion injury.¹⁰⁸ Although IRIs are primarily known to happen during medical emergencies like strokes, heart attacks, severe blood loss,¹⁰⁹ and compartment syndrome, CRPS and compartment syndrome are thought to be related in a somewhat inverted fashion. Where compartment syndrome is intense pressure over a short period of time, CRPS is low- to mid-grade pressure over an extended period of time, blocking the small blood vessels that deliver fresh oxygen and nutrients to our tissues and carry away waste. The longer and more severely this process goes on, the more backlogged the circulation becomes, adding pressure to the nerves, bones, and other tissues, and increasing the individual’s pain by causing the nerves to fire. 

The ischemic aspect blocks blood flow. During this stage, you may notice the skin looking pale, grayish, bluish, purplish, mottled, or cold. An individual may lose sensation or awareness of where that area is located in space, and they may feel numb or wooden; this is particularly likely to happen in colder environments once you start hitting the low 60s and especially in freezing weather with ice or snow. If this state goes on long enough, the tissues not receiving fresh oxygen become necrotic and die.  

To avoid this, the second aspect of the injury cycle comes into play and reperfusion takes place, making the blood vessels open extra wide so blood can be forced into the starving tissues. During this stage, you may notice the skin is hot, looking bright or dark red, blush pink, or vessels bulging; the person with CRPS may feel a pins and needles sensation or a numb area “waking up” as circulation returns to that location or burning as hot blood briskly changes the previously cold tissue temperature. Paradoxically, this rapid return of oxygen-rich blood is actually quite damaging to the starved cells and causes quite a bit of corrosion damage through oxidative stress via a chain of electron stealing; this phenomenon damages the integrity of the cell walls, making them weak, and harms cell homeostasis, structures, and functions.¹¹⁰

The IRIs in CRPS are thought to start in deep tissues and slowly move towards the surface as fluid builds up. This fluid applies pressure on the neurovascular bundle, which makes the nerves fire. We’ll talk more about this in another section, but this pressure also affects our bones, which is why our bones often hurt, a feeling I often describe as “being eaten by acid.” This fluid accumulation is also what is thought to increase the severity of allodynia, and as the swelling in the spaces between blood vessels and cells reduces, the allodynia (while it may not disappear) often reduces as well as the pressure the fluid applies to the nerves, which causes spontaneous firings, eases.¹¹¹

There are “hot” reperfusion-dominant cases and “cold” ischemia-dominant cases of CRPS. Many people start with a “hot” case with easily visible swelling and bright or dark red skin discoloration, but as time goes on, the swelling reduces and their skin becomes more “normal looking” and takes on a bluish, purplish, or pale tone as they switch to a “cold” ischemia-dominant CRPS case. The longer a person has CRPS, the more likely they are to become ischemia-dominant. This is standard and not at all unusual; it should not be mistaken for remission or a reduction of all symptoms (especially pain), but rather a natural progression of the condition. 

During the “hot” reperfusion-dominant phase is the time frame a person is the most likely to achieve remission, but not everyone does. Indeed, this study found that only 5.4% of CRPS patients were completely symptom-free 12 months after onset and that symptom reduction was greatest within the first six months¹¹²; the latter is a finding that is common across CRPS research. 

Some practical tips and tricks: 

• Cold tells our blood vessels to constrict; heat tells them to dilate. While ice is detrimental to CRPS and should always be avoided to protect the longevity of our nerves, something cool can encourage those whose vessels are experiencing reperfusion to constrict. On the other hand, those experiencing ischemia can utilize heat to encourage their blood vessels to expand. Hot pads, hot towels, warm water (you can even add some Epsom salts if you like; the magnesium will block the nerves’ calcium channels to provide some pain relief) can all be assistive. Wet heat penetrates deeper into our tissues than dry heat.  
• Dress in weather-appropriate clothing, even if you cannot feel the cold any longer. Those of us with CRPS can rapidly change our body temperature, so thin, breathable layers are a better option than one or two big, bulky pieces. Socks! High quality, sweat-wicking socks; some people find compression socks to be life altering, while others cannot tolerate them (I’ll discuss this more in the lymphatic section). Carrying around a pair of fingerless gloves and a hat or headband to protect your ears from the cold wind can be useful. A lightweight windbreaker to keep in your bag or car even during the summer can help if the weather changes on you rapidly, it starts to rain, or you need to go into a building that keeps their AC low; windbreakers compress well and don’t take much space. Heated vests can be especially helpful during the coldest parts of the year if you need or want to go out in the snow or ice for an extended period while keeping your core temperature up. 
• To help counteract the oxidative stress of reperfusion, eat foods high in antioxidants, such as beans, berries, pomegranates, potatoes, nuts, apples, plums, dark leafy greens, oats, and a variety of herbs & spices, like cinnamon, oregano, ginger, garlic, chili, turmeric, paprika, and sage.
• Exercise, particularly gentle aerobic activity, can help keep the peripheral blood vessels more dilated, preventing a deep rut of ischemic-driven disuse pain that is hard to escape.  
• Vibration is a vasoconstrictor, so car rides, loud concerts, and other similar stimulation can cause tightening of the blood vessels, which may increase pain.¹¹³
• Vibration-absorbing wheelchair cushions, memory foam pillows, or other dense or air-filled inserts or paddings can help reduce the unpleasant impacts of a moving vehicle’s vibrations on vasoconstriction. Additionally, it can help mitigate the amount of adjustments an individual exerts muscularly to compensate for the constant motion of the environment and a person’s own body.
• The IRIs in CRPS can be misdiagnosed as or comorbid with Raynaud’s phenomenon, though CRPS is a differential diagnosis to Raynaud’s.¹¹⁴ Treatment for Raynaud’s is targeted at reducing tissue ischemia and therefore relevant to CRPS as well. Nitric oxide, sildenafil, vardenafil, and tadalafil have all shown beneficial results for Raynaud’s, and Botox is also being explored due to reducing vasoconstrictive responses.¹¹⁵

Sudomotor & Edema: Swelling and Sweating

The third requirement in the Budapest Criteria is either sudomotor dysfunction or edema or both.¹¹⁶ This means sweating in the CRPS-affected area that is asymmetrical from other areas in the body or an overall change in the sweat baseline output from prior to the onset of CRPS or swelling in the CRPS-affected area. The individual needs to fulfill at least one of these subcategories, but can be experiencing all of them. 

The proper name for excessive sweating is hyperhidrosis.¹¹⁷ The sensory A-delta and C fibers are responsible for sending information relating to hot and cold temperature to the brain, which then increases or decreases sweat output to thermoregulate according to that information; in CRPS, these sensory fibers are highly dysfunctional, as are the sympathetic nerve fibers that control the sweat glands. This dysfunction might be limited to just the original location of injury or may spread to impact other areas through the bilateral innervation of the sympathetic nervous system. 

Those with CRPS may also notice an increase in their sweat output while under emotional stress or other stimulating events that activate the emotional and prefrontal cortex regions of the brain. Thermoregulatory sweating (to cool off) is accompanied by expansion of the blood vessel (which in CRPS usually means red or blushing tints to the skin and perhaps visibly bulging vessels) while emotional sweating (as a stress response) is accompanied by constriction of the blood vessels (which in CRPS usually means purplish, bluish, mottling, paling, or graying of the skin, perhaps with skin-under-nail color changes to match, and often being cold to the touch). There can also be an increase in sweat output while sleeping, digesting food, or while eating.

Swelling is thought to be the result of blood plasma leaking out of gaps in vein walls (known as “extravasation”) caused by dysfunctional endothelial cells^118,119,120 (which make up blood vessel tubes), allowing fluid to slip into the interstitial space between tissue cells instead of using the valve system to make it back to the heart and lungs, remaining in circulation. When enough of this plasma builds up over time, the swelling becomes noticeable, and the more there is, the more painful it becomes, causing more spontaneous nerve firing by applying more pressure and increasing hypersensitivity.¹²¹  

This build up blocks off more and more of the tiny vessels, compounding the issue. It does not take much exertion of external force to close off the small vessels and prevent blood from flowing out of the capillary beds, creating a vicious feedback loop. This fluid also puts pressure on the microvessels inside and surrounding bones and joints, causing a deep, aching pain (which will be discussed more in the Bones and Joint section).

But what about those with Persistent CRPS who don’t display much, if any, visible swelling anymore? Are they completely better? They say they still experience pain; are they exaggerating or lying?

Because of how common it is for those without visible swelling to be dismissed, delegitimized, undermined, disbelieved, and brushed off because their pain cannot be seen, I am going to pull a direct quote from a paper, which I believe I only do in two other sections in this entire series:

“The duration of the initial, edematous stage of CRPS-I is highly variable. Some patients remain in this state, have episodes of exacerbated edema, or progress to a non-edematous stage characterized by cyanosis and/or atrophy of subcutaneous tissue. Patients with slow-flow would be expected to exhibit edema, but there can be no plasma extravasation from leaky venules if there is no-reflow in their upstream capillaries. Thus, at later times, when no-reflow predominates, the patient would be in the cyanotic/atrophic phase. We propose that the progression from early-stage to late-stage CRPS-I reflects the evolving dominance of no-reflow over slow-flow in deep tissue capillaries. The variability in the progression from predominately slow-flow to predominately no-reflow is likely to be the basis of the argument over whether CRPS-I is a staged condition.”¹²²

Now there’s some pretty dense language in that quote, but in short it’s stating that, at the beginning of CRPS, swelling is expected as the capillary beds aren’t all completely clogged up and blocked off yet, but as the feedback loop establishes itself and more and more of the microvessels get either compressed, overly constricted, or blocked so that blood cannot pass through, then the veins downstream cannot leak that blood plasma that isn’t passing through out into the surrounding area and so the swelling greatly reduces. There may still be some swelling present, but they hypothesize that it would hide itself in deep tissues that wouldn’t be readily visible.

This should NOT be mistaken for CRPS going into remission! This is the natural progression of the condition for most people, and is in fact CRPS more firmly establishing itself in the nervous and vasomotor systems, not an omen of recovery. It is highly important to be able to tell the difference between genuine strides towards healing and improved symptoms and the ischemia-reperfusion injury cycle moving from reperfusion-dominance to ischemia-dominance.

Some practical tricks and tips:

• Lymphatic drainage/lymphatic massage is a technique to stimulate the lymphatic system to pick up fluid from the interstitial space outside of the blood vessels, reducing pressure that creates edema. While medical professionals like physical therapists can provide this treatment modality, it is also one that can be self-administered. 
• If your allodynia is too strong and touch is intolerable, let gravity start working with you instead of against you, particularly if your CRPS is in your legs. Reposition so that gravity helps push blood and fluid back towards your heart instead of pooling at your lowest point. 
• Compression socks, pants, sleeves, and gloves (though not everyone can tolerate the pressure) can help reduce the amount of fluid that can leak out and gather into the space outside of the vessels. These can be particularly helpful during extreme weather or high levels of physical exertion. 
• Reducing the amount of fluid applying pressure on the neurovascular bundle is thought to reduce the amount of skin-level hypersensitivity that those with CRPS experience. 
• Sympathetic nerve blocks can interrupt the excessive sweating nerve signaling. However, not everyone responds to nerve blocks,^123,124,125 and even those who initially do respond may become less and less responsive over time. SNB have a tendency to work best during the sympathetically-maintained pain stage of the condition, which usually lasts six to eighteen months, depending on the individual, but for some people SNBs work for years. If they work for you, expect relief to last anywhere from a few hours to a few weeks. 31-61% of CRPS patients experience relief with SNBs.^126,127,128 While they should not be utilized as a requirement for a diagnosis, lumbar paravertebral sympathetic blocks are recommended for those with lower limb CRPS and cervicothoracic block (aka stellate ganglion block) or upper thoracic sympathetic block is recommended for upper limb CRPS for those who wish to pursue this treatment modality.¹²⁹
• Wicking clothes can help pull sweat away from the skin. Breathable fabrics made of natural fibers like cotton, linen, muslin, chambray, bamboo, and silk can help during the heat of the warmer months. For colder seasons when you need something a little more thermally insulating but still want your sweat pulled away from your skin, Merino wool and wool, nylon, polypropylene, and micromodal are options to explore. 
• Sweating a lot can rapidly leave you dehydrated, particularly if you struggle with getting enough fluids in the first place. Drink enough water.
• Consider an electrolyte drink. If you cannot find one without added sugars or you’re tight on cash, they’re fairly simple to make at home. There are many recipes out there to tailor to your particular tastes, but the core of any electrolyte drink is salt. 
• If you’re someone who is not the person with CRPS, but notices that they are extra sweaty, you don’t need to point it out. They are aware. There is a good chance it makes them uncomfortable and leaves them feeling at least somewhat gross. You don’t need to draw more attention to it, especially in social settings and groups. If they seem dehydrated (particularly if it’s hot), you can offer to get them a water or a no sugar added drink, if you’re looking for a way to be more helpful.
• There are several pharmacologic therapies out there, as well as non-pharmacologic ones, that have been covered in-depth by the International Hyperhidrosis Society which can be helpful for CRPS patients. See more at www.sweathelp.org.

Motor & Trophic: Motor and Hair, Nail, Skin Changes

The fourth and final requirement in the Budapest Criteria is Motor and/or Trophic Dysfunction.¹³⁰ This causes problems with controlling voluntary gross and/or fine motor control and/or changes in our hair, nails, or skin. This can include signs and symptoms such as decreased range of motion, weakness, tremors, dystonia, fast or slow hair growth, hair loss in affected areas, brittle, ridged, spotted, or cracking nails, lunula that disappear, nails that grow rapidly or slowly, and thin skin, shiny skin, rashes, and ulcers. 

Other common motor complications include spasming and cramping, twitching (myoclonic jerks), dystonia, fasciculations, and slack (atonia/isolated cataplexy); you may also feel fluttering, though this more accurately falls under the Vasomotor section in my opinion, as I find this most often to be the rapid motion of blood vessels rather than a muscular sensation. 

Other trophic complications include neurodermatitis, folliculitis, spontaneous bruises, black and blue spots over the skin, thickening skin, dry skin, thinning skin (skin atrophy), flaking, thickening, deformed, or discolored nails, inflammation, and swelling that can imitate nerve entrapment syndromes.^131,132 Those with severe cases and exhausted immune systems can end up with serious infections that are long-lasting, can spread, and do not respond to standard treatment regimens.^133,134 If these infections are not appropriately treated, they can lead to very negative outcomes for the individual and even be life threatening. 

Those with CRPS can end up with both dystrophy and muscular atrophy. Dystrophy (as in ‘reflex sympathetic dystrophy’, one of the previous names for CRPS) and atrophy both cause muscle weakness and loss of muscle mass. This aspect will intertwine heavily with both the Energy/Mitochondria and Bone/Joint sections of this series.  

Some practical tips and tricks:

• CRPS is a use it or lose it condition. It is much easier to maintain the muscle mass and range of motion you already have than to get it back after it has been lost to disuse and muscle wasting. Physical therapy, gentle exercise, and movement are very important tools in the management toolbox for those with CRPS. While it is important to challenge ourselves, it is also key to respect our body’s boundaries, so that we do not activate our sympathetic self-protection system due to overactivity. The Comfort-Stretch-Panic Model can be a useful concept to keep in mind as you exert yourself.¹³⁵ Staying in the Stretch Zone for bursts of activity, retreating to the Comfort Zone to recover, then going out into the Stretch Zone again without overstepping into Panic/Distress allows us to, bit by bit, expand our circles, so that Comfort and Stretch grown and expand while Panic/Distress shrinks, giving us more space to explore and engage with the world with excitement, joy, pleasure, success, confidence, competence, and a willingness to take risks without anxiety. 
• Strengthen and stabilize joints, especially if you struggle with dystonia, involuntary contractures, and/or hypermobility, particularly if your CRPS is in your lower body. Having your joints perpetually twisted out of proper alignment is not good for the long-term outlook; this carries extra weight if you have to walk around on a painful limb with out-of-place joints. Pay particular attention to shoulders, knees, and especially hips, as the way our spine sits will impact our entire frame. 
• Aquatherapy can be a particularly useful and gentle aerobic physical therapy modality that offers resistance and reduces the amount of one’s own weight a person has to carry.
• Moisturize and hydrate. If you develop thin, dry skin (more likely with “cold” ischemia-dominant cases) that cracks and splits easily with little provocation, help bolster it by moisturizing and ensuring you drink plenty of water. If your skin is particularly sensitive or you find that lotions now have a tendency to sit on top of your skin instead of being absorbed, Jojoba oil is biomimetic, so it acts and functions like the oils our skin naturally produces while being very gentle.¹³⁶ Lanolin is also a natural biomimetic emollient used to repair the skin barrier, keeping water in and foreign bodies out;^137,138,139 additionally, lanolin can also be used as a base for topical medication delivery for compounded topicals.^140,141 Keep some chapstick or other lip protectant easily accessible for those with cracked, bleeding lips or who struggle with staying properly hydrated, which can be challenging for those with overactive bladders.
• Some individuals find that anticonvulsant medications are particularly assistive for the motor dysfunction (and some of the burning pain and migraines as well); this class includes gabapentin/Neurontin, pregabalin/Lyrica, carbamazepine/Tegretol, clonazepam/Klonopin, and topiramate/Topamax, among others. These medications do have side effects and can be difficult to discontinue. While many people with CRPS can find moderate-to-immense relief with anticonvulsants, this class of drugs should be considered with full awareness of possible side effects. This class may affect weight (either causing gain or loss), or cause dizziness, fatigue, headaches, mood changes, issues with coordination and balance, nausea, blurred vision, or impaired thinking and cognition. Lyrica, gabapentin, and Topamax (“Dopamax”), in particular, have established reputations for impairing cognitive functions to varying degrees in a significant percentage of users.^142,143,144
• Cataplexy (usually happens with narcolepsy, but can be isolated)^145,146 involves the orexin neurotransmitter system, the hypothalamus, and the sympathetic control center of the locus coeruleus. Cataplexy leaves a person with significantly weakened or no control over their voluntarily controlled muscles for a short period of time while they remain fully conscious, typically triggered by experiencing a strong emotion; it may be mistaken for a seizure. Cataplectic attacks vary in frequency and severity and are thought to activate the neurological systems that keep us immobile during REM while we are awake. The orexin system is also implicated in neurological disorders, depression, insomnia, ischemia-reperfusion injuries, addiction, and Alzheimer’s disease.¹⁴⁷ Current treatment for cataplexy is largely symptomatic: understanding the mechanisms, monitoring and moderating strong emotional spikes, with antidepressants and sodium oxybate being the most effective medications.¹⁴⁸

Bones & Joint Pain: Thinning, Twisting, and Hypermobility

Those with CRPS often state that their bones and joints hurt. They may compare the feeling to: extreme compression to the point that they are afraid their bones will break, deep aching, acid eating the bones from the inside, or bones being both brittle and heavy simultaneously, among other sensations. They may feel like carpenter ants are chewing through their sinews or that their tendons and ligaments are dried out leather twisting and cracking to the snapping point or so stiff that they cannot bend the joint affected or only very slowly, with great pain and difficulty. They may experience fractures from seemingly small injuries, particularly in the wrist and the outer edge of the foot,¹⁴⁹ as well as in fingers and toes.  

It is thought that due to the microvascular dysfunction and the ischemia-reperfusion injuries discussed in the Vasomotor section,^150,151 the bones in the IRI-affected area can be negatively impacted. Individuals with CRPS can display bone mass loss known as osteopenia or osteoporosis with abnormal bone cell turnover and resorption through increased osteoclast activity, demineralization, altered bone microstructure in spongy bone near joints, and abnormal bone metabolism.¹⁵² In the long bone shafts (cortical) and spongy bones near joints (trabecular), individuals with CRPS can show remodeled and altered bone structure and density.^153,154,155 Additionally there is evidence of blood plasma leakage, venous dilation, the simultaneous thickening of arteriole walls and shrinkage of the lumen, and bone marrow vascular dysfunction, which can cause the bone marrow/fat to die or be damaged; this is problematic as bone marrow is where our red and white blood cells are produced.¹⁵⁶ 

Patients also reveal tissue swelling in and around joints, bursa, osteoporosis or osteopenia, and the reduction of bone that is directly beneath the protective cartilage padding in joints.¹⁵⁷ While joint problems in CRPS are a multifaceted issue of ligaments, tendons, muscles, and bones, it is often the soft tissue atrophy that actually drives this problem initially. However, if there is a maladaptive response and appropriate corrective measures are not taken, then this can lead to a true joint problem later down the line, as the contracting muscles pull the joint out of place for an extended period of time. This is particularly true for the large subset of individuals who have comorbid EDS/hypermobility, who rely heavily on their muscles instead of their sinews to hold their joints in socket.^158,159 Joint pain often increases with cold, damp, wet, or wintery weather, as the barometric pressure shifts and blood flow and activity reduce and swelling increases, activating mechanoreceptors in the C and A-delta fibers.

Some practical tips and tricks:

• Some people find a helpful diagnostic tool in the Three-Phase Bone Scintigraphy, while others have better results with Digital Infrared Thermography Imaging, if you’d like additional evidence to support the Budapest Criteria.¹⁶⁰ Not everyone with CRPS will show positive results with the Three-Phase Bone scan, and while almost everyone with CRPS will have a positive ITI result if you can catch them during an ischemia-reperfusion injury cycle, doctor visits and temperature dysregulation don’t always align. 
• Bisphosphonates suppress osteoclast activity and reduce bone resorption and as such have become a common drug in the toolbox used to treat CRPS, though there is some controversy on its effectiveness and adverse effects.¹⁶¹ 
• Bones need to be used to remain structurally strong. CRPS is a use it or lose it condition. Disuse dystrophy and atrophy are real complications to consider and actively work to counteract. 
• Moving slowly is better than not moving at all. Walking with mobility aids is better than not using mobility aids and not walking. Use the tools available to you to maintain your independence and activity to keep your bones as strong as you can for as long as you can. 
• If a fracture or break occurs and a brace or long-term structural support of some sort is necessary to help the bone heal properly, an Aircast or other removable option is a far superior option to a hard, plaster cast that cannot come off and will keep the limb locked in an immobile position, more prone to ischemia and poor proprioceptive signaling. 
• If muscle contractures are pulling joints out of place, strengthen the muscles to stabilize the joint. Leaving the joint in the wrong place long-term can cause many down-stream issues, particularly when it comes to the hips and shoulders and how they cause the spine to become improperly aligned. 
• When walking, it can be easy to tune out from your body to try to “power through” and allow joints to go wonky. Check back in with yourself occasionally and deliberately correct your posture and stride as much as you can, particularly if your CRPS affects your lower limbs. Practice doesn’t make perfect; practice makes permanent. Practice what you are doing deliberately and consciously to protect your long-term health. 
• Gently stretching and strengthening contracted, atrophied muscles can help relieve joint pain by addressing what is usually the cause of joints becoming stiff and distorted and putting tension on the tendon holding the muscle to the bone at the joint.

Chest Pain & Blood Pressure: Deep Radiating Pain, Orthostatic Intolerance, and Hypertension

Those with CRPS can experience both sensory and motor dysfunction when it comes to the heart, lungs, blood pressure, and chest pain. 

Those with CRPS who report chest pain do not generally attribute this discomfort to their pain disorder due to the deep nature of the pain, with less than half reporting it matching the standard burning, sharp, aching pains typical of CRPS. The majority report radiating pain that is bilateral, above the breast, and that lifting of the arm elicits pain. Half of the patients in this study were concerned enough about their chest pain to seek out medical care which included cardiac workups; 84% of these cardiac workups came back negative for heart-related problems. The leading hypothesis for this atypical chest pain in CRPS patients that mimics typical chest pain indicative of heart problems is sensitization of the intercostobrachial nerve and connected brachial plexus and nerve root T2. It is thought that movement of the arm, particularly lifting, stretches the brachial plexus and places traction on the intercostobrachial nerve, which runs through the front side of the rib cage, under the armpit, and down the inside of the upper arm.^162,163 Those with CRPS can also develop dystonia in the chest wall, causing difficulties in taking deep breaths with full lung expansion.¹⁶⁴

When it comes to the heart functionality, individuals with CRPS display an increased heart rate, a reduced heart rate variability HRV, and an inability to protect their cardiac output during orthostatic stress (changing positions, particularly going from laying down to standing up) which was associated with the duration of the condition and may lead to dizziness, lightheadedness, poor balance, inability to regulate blood pressure, needing to resume the prior position and try again more slowly, the feeling of being about to faint, or actually losing consciousness due to insufficient blood flow to the brain.¹⁶⁵ These results reveal a general autonomic imbalance and suggest a sustained stress response in CRPS patients.¹⁶⁶ Those with lower limb only involvement are more likely to pass out for POTS-related reasons than those with upper limb only or full body involvement; those with CRPS in general are 4.5 more likely to test positive on a Head Up Tilt Test than matched controls.^167,168 

As CRPS becomes more chronic, Postural Orthostatic Tachycardia Syndrome POTS, Orthostatic Hypotension, Hypotension, and Orthostatic Tachycardia can become more common. POTS, OH, and OT all cause the heart to work harder to compensate for the blood vessels’ lack of quick responsiveness in changing size to appropriately keep an adequate amount of blood flow to mandatory organs, like the brain. Under “good enough” circumstances, the autonomic nervous system will coordinate the function of our heart and vasculature to tighten and relax our vessels depending on our posture and activity level, so that our heart doesn’t have to over-exert itself; in the case of those with well-established CRPS and an exhausted autonomic nervous system, the heart has to work extra hard to compensate for the endothelial and vasomotor dysfunction in the circulatory system.^169,170 However, in the earlier stage of the condition, hypertension is more likely to be seen.^171,172,173

Some practical tips and tricks:

• If you’re experiencing chest pain with CRPS that aligns with the description in the referenced paper, don’t be surprised if cardiac testing you undergo comes back negative.
• On the other hand, not all pain is CRPS-related and it can be worth getting checked out, just to be sure it isn’t a structural issue that can be addressed before it becomes a major problem. Having reduced heart function due to a heart attack will not serve us in the long-term, particularly when taking the ischemia-reperfusion injury cycles into account.
• For essential and labile hypertension, many with CRPS take alpha blockers and calcium channel blockers. Do be aware that as the condition impacts a person longer and longer, hypertension is likely to eventually become hypotension for many people. 
• For hypotension and related orthostatic intolerances, midodrine is often a first-line medication, as it is not a mineralocorticoid like fludrocortisone, which can be poorly tolerated in long-term for hypotensive disorders, particularly in older patients.¹⁷⁴ 
• For hypotension, increasing salt intake is generally recommended. 
• For elevated heart rate, working on activating the vagal brake to help reduce sympathetic activity and increase parasympathetic activity.^175,176,177 Some providers may also recommend medications like beta blockers, combination alpha/beta blockers or calcium channel blockers to reduce heart rate.  
• Slowly changing positions gives blood vessels more time to adjust with less strain on the heart; stabilizing with walls, chairs, tables, and mobility aids can help prevent falls from lightheadedness and poor balance. 
• Temperature extremes (whether hot or cold) can cause blood pressure difficulties for those with CRPS, particularly if they are experiencing some sort of orthostatic intolerance.
• Gentle exercise can help keep the heart in shape and ready to meet our needs, despite reduced vascular capabilities. Aerobic exercise is recommended for neuropathic pain to reduce its intensity and neuroimmune components.^{178,179,180,181,182,183}
• For those seeking medical care, especially those with their cardiac workup testing coming back negative, getting a referral to the cardiology department’s electrophysiologist is likely your best bet. These specialist doctors focus on electrical dysfunction within the cardiovascular system and irregular heart rhythms; they regularly see dysautonomia and POTS patients. If standard cardiologists are plumbers, EPs are electricians, and they are more likely to be educated and understand CRPS patients’ needs due to autonomic dysfunction, even if they aren’t educated on or aware of CRPS itself.

Gastrointestinal: Intestinal Pain and Dysfunction

Some individuals with CRPS develop gastrointestinal issues; these can take place anywhere along the GI tract. CRPS patients regularly experience constipation, nausea, vomiting, diarrhea, indigestion, IBS, difficulty swallowing (dysphagia), and GERD.¹⁸⁴ Many may have difficulties breaking down the food they eat, extracting and absorbing nutrients from that food, or have issues with appetite and hunger. 

In patients with longstanding CRPS of usually five years or more with generalized cases that started in the lower body, gastroparesis (delayed emptying of the stomach) is a frequent complication and frequently co-occurs with urological symptoms, early satiety, and bloating.¹⁸⁵

Those who experience regular diarrhea may notice a whitish mucus in the toilet bowl; this is the intestinal lining that houses our gut microbiome and it is not something we are supposed to shed in large amounts.  If your intestinal mucosa is something you are excreting on the regular, you will likely also be experiencing other problems and pains with digesting food, as the organisms that help digest what we eat are no longer inside your body in large enough quantities to do their jobs in the way that is necessary. The sympathetic nervous system plays a direct role in the destruction of the intestinal mucosal barrier.^186,187

The sympathetic self-protection system directs our energy, attention, and resources to threats, defense, escape, attacks, and mitigating damage. It isn’t much concerned with digesting that meal you ate for lunch; that is the parasympathetic and enteric systems’ domain. When we live in a state of sympathetic-dominance, we can experience an array of difficulties with our digestive system. The more active our sympathetic system is, the less active our guts are.¹⁸⁸ Finding ways to encourage the parasympathetic system to become more engaged and activated before eating can assist in better digestion and hunger signaling.

Some practical tips and tricks:

• Explore the MIND [Mediterranean-DASH Intervention for Neurodegenerative Delay] diet, which focuses on brain health, neuroprotection, and the preservation of cognitive function.¹⁸⁹ In one study, those in the top third who adhered most closely to the MIND diet had a 53% reduction in Alzheimer’s compared to those in the bottom third who did not, and those in the middle third had a 35% reduction in AD compared to the bottom third.¹⁹⁰ MIND guidelines include vegetables (particularly dark leafy greens), nuts, beans, berries, poultry, fish, whole grains, and olive oil. They exclude items high in saturated and trans fats, pastries and sweets, red meats, cheeses, and fried foods. 
• Other diets to consider are the Mediterranean, DASH, FODMAP, 4Fs, Autoimmune Protocol, and Elimination.
• Know how amino acids in protein sources become our neurotransmitters, providing more or less power to different subsections of our nervous system. Pay particular attention to tyrosine and phenylalanine, which becomes our catecholamines and powers the sympathetic nervous system, and tryptophan, which become serotonin and powers our parasympathetic nervous system. Catecholamine-precursors can be found in large amounts in red meats, hard, aged cheeses, and alcohol.
• Work with the seasons. If you struggle to eat solid foods, particularly during the heat of the summer or the cold of the winter, try to think creatively to meet your nutritional needs. Summer smoothies and winter soups can be easier ways to drink calories if dense foods turn your stomach. 
• Consider protein powder, nutritional supplement drinks, and (if cow dairy is off the table for you) soy or nut milk as ways to get more protein if you are struggling to meet your nutritional needs. 
• Many people with CRPS have issues with their intestines not properly absorbing nutrients or appropriately breaking down their food. A dietician may be able to assist you in ensuring you are getting enough calories while meeting your nutritional needs. 
• Cooking can be a struggle. Meal prepping and crockpot dinners can be life savers, especially when the easy and standard grocery store frozen meals are often highly processed. Pre-made snacks, cooking in bulk then eating leftovers, and eating the individual components of meals without the labor of putting it all together can each help reduce the workload to ensure you’re still able to eat when you don’t have the energy to prepare a full meal. If you have someone willing to help you cook or make meals for you, be willing to accept help from people who care for you, so long as they are taking your dietary needs into account. 
• Prebiotics and probiotics can help replenish a gut microbiome that has been unbalanced.^191,192,193 Look for live, multi-strain, high CFU options. Greek yogurts can be great sources of live probiotics and tryptophan (which becomes serotonin), and fermented foods and drinks like kimchi, kiefer, and kombucha are also probiotic-rich. 
• Some lightweight, gentle touch can help activate parasympathetic and enteric nerves to help aid in digestion and increase peristalsis (the rhythmic squeezing motion of the guts that moves food down the tube). This is known as abdominal massage or visceral massage or bowel massage.^{194,195,196,197,198,199} It is best done lying down and can be self-administered or provided by a healthcare professional like a physical therapist.
• Magnesium-rich foods can provide an additional avenue of pain relief. In neurons, the magnesium receptor and the receptor where ketamine binds sit directly on top of each other in the same calcium channel. While magnesium does not provide the same neuroplastic effects as ketamine, it can provide pain relief by reducing neuronal firing.
• Worthy mention:  oats, quinoa, buckwheat, and amaranth. These are magnesium-rich, naturally gluten-free cereals that are also a fair source of protein, carbs, and fiber. They also contain tryptophan and several B vitamins. These flexible grains can be eaten in a variety of ways from cookies to granolas to overnight oats and more traditional oatmeals to breads and noodles. There are also gluten-free flours from almond meal, potato starch, rice flour, arrowroot, teff, chickpeas, tapioca, and other foods that can replace the inflammatory gluten,^200,201 if you choose. Many of the “sweets” that those with CRPS often cut out due to the sugar and gluten content can be replaced with homemade versions that use honey or other non-sugar-based sweeteners and gluten-free flours.

Genitourinary: Bladder and Reproductive Organs

Individuals with CRPS may develop issues in the pelvic area, either with the reproductive system or the urinary system. 

There are some who propose Chronic Pelvic Pain CPP as a form of CRPS.^202,203 There is difficulty gaining traction for this viewpoint as many medical professionals believe CRPS can only affect limbs and, due to the anatomy of the pelvic area, applying the Budapest Criteria to this location cannot be done in the same manner as an extremity. However, the sensory, vasomotor, sudomotor/edema, and motor/trophic symptoms can be present in the low abdomen. 

Those experiencing such symptoms may find that they experience pain from intercourse, sitting, rubbing legs, and underwear, hosiery, and tight fitting garments. The vagina and uterus are lined with endothelial cells, which coat mucosal cavities in humans and which are dysfunctional in those with CRPS.^204,205,206 Those with CRPS are also 5.3 times more likely to have a menstrual disorder than comparable controls and will often experience pain flares in sync with their cycle.²⁰⁷ Others may develop amenorrhea (an absence of the monthly period cycle in non-pregnant, non-postpartum, non-menopausal adults that lasts at least three months). Due to the cyclical nature of menses and the hormonal fluctuations that accompany it, CRPS pain and dysfunction can vary widely for those who menstruate throughout the course of their cycle, as opposed to those whose sexual/reproductive hormonal levels remain more steady; some may find that hormonal birth control may be assistive in reducing flares associated with menses.

Some people with CRPS go into remission or find their symptoms are greatly reduced during and after a pregnancy. However, this is not a guaranteed outcome, and you’ll have a child to care for in the aftermath, which is a lifelong commitment. If you desire to be a parent and are in a place in your health journey, mental stability, economic outlook, and life where that is a viable option for you, more power to you, but please think through the full two decade period of raising and parenthood you’re signing up for before pursuing a pregnancy in attempts to achieve a potential remission. Also consider that many medications cannot safely be used during gestation and will need to be stopped while carrying and breastfeeding.^{208,209,210,211}

If you know you do not wish to get pregnant in the near future or ever, consider your long-term and permanent birth control options. For those seeking permanent, minimally invasive sterilization, a bilateral salpingectomy will completely remove the Fallopian tubes via laparoscopic surgery; a vasectomy can be done in office with no sutures needed, typically in under 30 minutes.

While those with uteri are more often affected at a rate of 3-4 to 1, let’s not overlook the other group in this equation; CRPS can also affect testicles, scrotums, perineums, and penises.^212,213,214 CRPS in these areas can cause intimacy or self-pleasure challenges, erectile dysfunction, pain with sitting, standing, and moving the legs, feeling the need to regularly readjust or not feeling able to tolerate the touch to readjust despite a need to do so, or concerns of testicular torsion that come back with negative test results. Due to the disproportionate sex ratio in CRPS, finding a urologist who understands (or is willing to learn) how CRPS can impact the male genitourinary system can be a challenge; however, finding such a doctor will become more and more imperative as the individual with CRPS ages and routine health checks for things like prostate issues and certain cancers becomes more important. Having a knowledgeable urologist will ensure the patient can still receive the necessary care without being in pain that could have been avoided by an informed, compassionate doctor. The skin of  the genital area is thinner than almost any other external area of the body to begin with, so skin atrophy here is more likely to be significant when circulation is impaired. Doing regular self-checks to monitor the skin health and maintaining hygiene with gentle products in this area is important to act preventatively and be able to act promptly on any issues as they arise.

The bladder is another common cause of concern and dysfunction. Those with this symptom may experience increased frequency, a strong urge to urinate, increased nighttime urination, an inability to hold their urine for extended periods or perhaps even incontinence.^215,216,217 They may have difficulty getting their bladder sphincters to expand due to the heightened sympathetic activity, causing issues with urine retention, incomplete voiding, and needing to go to the bathroom again shortly after using the toilet.²¹⁸ While many may be familiar with the burning sensation of a UTI, those with CRPS can experience a similar burning sensation due to dysfunctional nerve signaling; this is often tied to urine release, but does not “get better” with time like UTIs do; the individual simply adapts to their new reality, though they may be able to reduce the intensity of the dysfunction and frequency as they calm the activity of their sympathetic nervous system. 

Even if the individual has greatly expanded their personal mobility, needing regular access to a toilet can create a “leash” that makes people hesitant to go too far from a bathroom they feel comfortable using. While being in the car in general can be very painful due to the vibrations and limitations of movement, taking long trips is also difficult for those with overactive bladders due to their frequent need or urges to urinate, and so if a road trip is necessary, plan on working regular pit stops into your itinerary for bathroom breaks and stretching for improved circulation for increased comfort and reduced pain and stress.

There can be an inclination to limit water and fluid intake to reduce the amount of urine one will pass in a day. While it may be effective at reducing the frequency of bathroom visits, it will be detrimental in multiple other ways. Dehydration is not the answer to an overactive bladder. This reduces blood volume, allows inflammatory particles to build up, lowers blood pressure, increases heart rate, dizziness, headaches, muscle cramps, constipation, skin problems, mood swings, fatigue, and confusion. 

Some practical tips and tricks:

• The “Skin Turgor Test” is when you lightly pinch your skin for about three seconds to see your skin’s elasticity and if you’re too dehydrated. This test is recommended to be performed on the back of the hand, under the collarbone over the chest, or on the abdomen. If your skin remains mounded up and is slow to return to its usual flatness, more water should be consumed.
• For bladder issues, pain during intercourse, and pelvic floor instability, pelvic floor therapy and exercises can help offer more conscious control over those muscles. The double voiding technique can be useful to reduce the feeling of having to turn right back around and go directly back to the toilet after standing up and walking away. Bladder training is slowly training your body by waiting after an impulse to urinate is felt and deliberately increasing the time interval (if possible) as weeks and months pass. In some cases, medications may be preferred or necessary. 
• Caffeine and alcohol can irritate a neurogenic bladder. Some people find Gosha-jinki-gan, cleavers, horsetail, mint, chamomile, or lavender teas to have a calming effect on their bladders. 
• Stimulating the parasympathetic nerves in the sacrum area at the low back that run to the bladder with some gentle touch may help encourage the sphincter to relax and allow urine to release for those with difficulties voiding. 
• For those with vulvodynia/pelvic pain, intimacy can be a struggle and one that not everyone wants to undertake. However, if you’re looking for a way to help reduce allodynia so you can engage in sexual intimacy with a partner (or even some self-pleasure), topical creams or sprays such as lidocaine or compounded ketamine can offer a solution to taking the edge off the pain.
• If you’re open to engaging in intimacy while under the influence, cannabis or the federally-legal and synthetic pharmaceutical THC product Dronabinol can also provide a great deal of relief if consumed or inhaled.

Mitochondrial Dysfunction: Lack of Energy and Deep Exhaustion

“The mitochondria is the powerhouse of the cell!” You may remember this phrase from your days in school; it’s going to be useful to recall here. The mitochondria is like a generator inside each cell turning glucose into energy with the help of oxygen. These little energy packets are called ATP, and we use them to do all kinds of things required to live, including transporting molecules across cell membranes, muscle contractions, blood circulation, nerve transmissions, and growth and repair, among other uses. 

When we have enough oxygen for the mitochondria to function properly through aerobic respiration, one glucose molecule can provide 30-38 net ATP for us to spend on the tasks of living. But remember, people with CRPS have ischemia-reperfusion injury cycles and often don’t have enough oxygen in the tissues of their CRPS-affected areas.^219,220

This leads to anaerobic respiration that does not require oxygen or mitochondria to produce energy. This is far less efficient, producing only 2 net ATP per glucose molecule, as well as lactic acid as a by-product. Those with CRPS regularly have increased lactate levels in affected areas, which is presumed to be due to hypoxia from oxygen being unable to reach the tissues and anaerobic energy production.²²¹ High lactate levels can cause lactic acidosis, which adds an additional layer to an already unpleasant situation. Research also reveals a significant increase in muscular phosphate levels, which may be caused by diminished oxygen utilization.²²² High phosphate can pull calcium, leading to weakened bones. Reactive oxygen species, which are present during the reperfusion stage of the IRI cycle, damage mitochondrial proteins in those with CRPS, leading to reduced energy production and damage to muscle tissue.²²³

Many people with CRPS struggle with feeling like a burden or like they are lazy. They can no longer do the things they once could. A trend I’ve noticed in the CRPS community is that most of us are what I would label “hyper-independent overachievers.” Learning to adjust to this new reality of limited energy can be a severe challenge, especially if you placed your self-worth on what you could accomplish independently of others. Now getting the groceries done can leave you exhausted; even doing the dishes can wipe you out. 

I want to put this in context. If you are primarily “cold” ischemia-dominant CRPS with poor oxygen utilization, you are running on anaerobic ATP production a lot of the time in affected areas. 2/30=0.067. 2/38=0.053. When we are using non-oxygen-based energy production, we are running at 5.3%-6.7% energy efficiency. Show yourself some grace and compassion. You aren’t being lazy; you have limited resources, and you need to be judicious how you spend them. That is reality. 

It can be easy to talk nastily to ourselves or let others be mean to us about how our productivity has gone down. It can be a simple thing to be harsh, critical, and rude in our own minds about the things our bodies can no longer accomplish and how we feel it holds us back, especially if we have previously used mental pathways of disdain and contempt for ourselves. I urge you to be kind and understanding about what is actually going on, creating buffer zones to allow yourself more time to finish necessary tasks and asking yourself if that item on your To-Do list is really something that needs to get done and, if it is, are you the one that has to do it or can it be delegated to another person. 

Critical, denigrating self-talk will activate the sympathetic nervous system, which is counter-productive if our goal is a ventral vagal parasympathetic state. Psychologically punishing yourself may feel “good” or “appropriate” in the moment to “challenge” you to meet your previous standard of output, but it is not a neurobiologically sound approach for long-term health and wellness when it comes to managing and mitigating CRPS. 

Some practical tips and tricks:

• With the anaerobic energy production, lactic acid, and substance P that circulate in high levels in those with CRPS, we often have trigger points or muscle knots. Manual myofascial release, trigger point release, trigger point injections, or dry needling (if you can tolerate it) can help release these “capsules” or “bubbles” of irritating, inflammatory chemicals that reduce circulation and increase muscular tension, contractions, and pain. Low-level laser light therapy LLLT can also be assistive in relieving myofascial pain and decrease trigger points.^{224,225,226,227}
• Understand that those with CRPS, especially “cold” ischemia-dominant cases, have reduced energy production in CRPS-affected areas and are regularly only producing 5-6% of the energy a healthy person makes from each glucose molecule; this can leave us exhausted and make it extremely difficult to go about the tasks of daily life or special events that require lots of effort and attention.
• The brain is an energy hog! Thinking takes a ton of energy, and when combined with the functional and structural changes to the brain we’ll discuss at the end of this series, the mental load of planning and executing can cause those with CRPS to run into barriers that can lead to flares or emotional dysregulation. 
• B Vitamins, riboflavin and cyanocobalamin in particular, and Vitamin C can help boost energy, as well as act as antioxidants. 
• Check in with your energy levels. Does this task NEED to be done? Does this task need to be done BY YOU? Does it need to be done by you TODAY or can it wait? 
• Block by time, rather than by task. Instead of working on a project until it’s finished, set aside a specific amount of time for work on that project, either with a particular end time or a particular end point, then stop. Don’t push yourself to keep going beyond your pre-determined finish point or time. It doesn’t need to get done all at once; you can come back and work on it more later, after your body and mind have had a chance to make some more energy and recover from the dedicated expenditure of the previous task. 
• Think like a powerlifter or a sprinter. You’re using anaerobic energy production. The anaerobic athlete demonstrates explosive strength and power for short bursts.
• Train like a marathoner or a cycler—not literally, of course. We want to shift our bodies into aerobic energy production as much as we can, so that we can reap the benefits of more efficient ATP respiration. The aerobic athlete demonstrates endurance and resists fatigue for extended periods. Gentle aerobic exercise can help get our circulation working better and, by extension, also increase our energy production. 
• Moving hurts, and not moving hurts more. Work like the heart: exerting without reaching the point of exhaustion and resting in approximately equal measure throughout the day while changing positions often.²²⁸ Resting and/or staying still too long is just as, if not more, harmful than being too active due to the vasoconstriction brought about by staying in one place and having no proprioceptive input to increase circulation to that area.²²⁹
• Give yourself permission to rest. As we make intentional choices towards our goals, allow yourself to choose replenishment, recovery, recuperation, and rest. Just don’t stay completely still too long to prevent your vessels constricting and starting the ischemia-reperfusion injury cycle; little movements or external proprioceptive stimulations to keep the blood flowing while you relax and recover are massively beneficial. Try to prevent your body parts from “falling asleep” while you do. 

Immune System: Autoinflammation and Autoimmunity

There are three subsections of the immune system CRPS impacts: the innate, adaptive, and microglial systems. 

The innate or nonspecific immune system produces what we consider to be the general inflammatory response. In CRPS, the most relevant aspect of this is proinflammatory cytokines.^230,231,232 Cytokines are a broad group of signaling proteins that can cross cell membranes and increase inflammation; they have various names, like interleukines, interferons, chemokines, tumor necrosis factor, and colony stimulating factors. Those with CRPS often have increased levels of proinflammatory cytokines, creating an inflamed state in the individual’s tissues.^233,234

In autoinflammatory conditions like CRPS, the innate immune system becomes dysfunctional and abnormally activated, resulting in a flood of cytokines that lead to inflammation without a readily apparent cause such as an infection. Particularly in the early stage of CRPS, inflammation is often easily visible with significant swelling, heat, reddening, and pain, with increased levels of pro-inflammatory cytokines TNF-a, IL-1β, IL-6, and ET-1 and decreased levels of anti-inflammatory cytokines IL-4 and IL-10.²³⁵ Mast cells have been found to proliferate and activate in acute CRPS patients.^{236,237,238,239,240,241,242,243} Langerhans dendritic cells are found to be abundant in early stage individuals, though in longer-standing cases the numbers significantly reduced.^244,245,246

The adaptive or specific immune system produces what we consider the autoimmune response. In a considerable subsection of patients with CRPS, there are autoantibodies against autonomic nervous system receptors that are responsible for sympathetic responses: adrenergic alpha-1a and beta-2, which also damages endothelial cells as a result.^247,248,249 They also target muscarinic-2 receptors,²⁵⁰ which are located in cardiac tissue and slow the heart rate.²⁵¹ The adrenergic receptors work for smooth muscle contraction and relaxation and vasoconstriction and vasodilation; when they get “eaten” by the immune system, the ones that are left become more sensitive and hyper-responsive to circulating neurotransmitters (like catecholamines, such as noradrenaline) to compensate. The Alpha-1a receptor is also involved in cognitive functioning, such as memory, learning, and mood.

Autoantibodies sensitize pain neurons (A and C fibers), causing significantly increased nociceptive activity and spontaneous nerve impulses.²⁵² Due to the importance of understanding that at its core, CRPS is likely an autoimmune condition, other journals on CRPS and the adaptive immune system have also been included below.^{253,254,255,256,257,258,259} Leading researchers and scholars for CRPS have proposed the term IRAM for the condition: Injury-triggered, Regionally-restricted, Autoantibody-mediated autoimmune disorder with Minimally destructive course.²⁶⁰ Others have proposed creating a new category of disorders called Autoimmune Autonomic Dysfunction Syndromes that includes CRPS, Fibromyalgia, Post-COVID Syndrome, Chronic Fatigue Syndrome, and Silicone Breast Implant-Related Symptoms.²⁶¹

Finally, the brain’s immune system: the microglia. Microglial cells in their healthy form provide vital functions to a properly functioning central nervous system, offering protection, repair, and regulatory support for neurons while removing toxic waste, invaders, and dead or dying cells. However, they are also the primary source of inflammation in the brain and, when they stop recognising the self, they can attack healthy cells.²⁶² In CRPS, the microglia become “activated” against the self and are one of the major causes of central sensitization in persistent CRPS.^263,264 The neuroinflammatory state in the nervous system caused by the activated microglial cells can spread and does not have to remain localized where it started.²⁶⁵ We will discuss the changes in the brain in considerable detail near the end of this Primer; however, a broad array of areas are impacted including locations that control somatosensory function, autonomic function, cognition, memory, motor function, attention, pain modulation, and bodily experience and interoceptive integration.²⁶⁶

Some practical tips and tricks:

• Some people find immunomodulators (such as glucocorticoids, anti-rejection drugs, disease modifying anti-rheumatic drugs DMARDs, tumor necrosis factor-α antagonists, thalidomide, and immunoglobulins) to be useful.^267,268
• Others find moderate to high powered NSAIDS, COX-2 inhibitors, and adrenocorticotropin hormones helpful to assist with anti-inflammatory and auto-immune responses.
• Low-dose naltrexone can be quite assistive in down-regulating the microglial activity.^269,270,271 It helps reduce the autoimmune activity in the central nervous system and increases the body’s naturally produced painkillers called endorphins. Do note that naltrexone is an opioid antagonist and cannot be taken with opioid agonists (such as oxycodone, hydrocodone, codeine, kratom, morphine, and tramadol). Naltrexone at its full dose (50mg) is used to help prevent relapse in those with opioid use disorder; low dose naltrexone is less than one-tenth of that (<5mg). For those who may struggle with OUD, who have a personal aversion to opioid agonists, whose doctors are unwilling or unable to prescribe agonists, who find that agonists do not assist in relieving their pain, or who would prefer to move away from agonists for other reasons, LDN can be a fantastic option that is usually quite low cost, even if you have to pay full price out-of-pocket at a compounding pharmacy. 
• Cannabis is also a microglial modulator and suppresses immune system activity.^{272,273,274,275,276,277} For those with autoimmune conditions, this can be helpful. Those with chronic pain generally find that indicas are more relieving than sativas. If you prefer edibles, watch out for that sugar content! Rick Simpson Oil RSO is a highly concentrated oil that can be eaten in extremely small quantities (think a grain of rice) for a multi-hour high; it is usually sold in syringes, if you are in a legal state. If you are new to cannabis (or still not super sure of your way around the cannabis industry), talk to your local budtenders; they are usually highly knowledgeable and often more than willing to share the information they have learned to help you find the best product for your situation.

Endocrine System: Neuroendocrine and Hormones

Our hormonal levels are an important aspect of a properly functioning person. The amount of hormonal secretions released are controlled by a feedback loop system that originates in the brain with the hypothalamus and pituitary and then travels to the target organ (such as the thyroid, liver, adrenals, ovaries/testes, and kidneys). The hypothalamus directs the pituitary when to release and the pituitary directs the target organ when and how much to release, then those hormones eventually make it back to the brain (among other CNS stimuli), creating a feedback loop. These hormonal feedback loops are called hypothalamic-pituitary axes.  

In CRPS, the hypothalamus is dysregulated, so any and/or all of the axes controlled by this region of the brain can become dysfunctional. The one that is probably the most easily recognizable in this condition is the HPA axis that runs to the adrenal glands on top of the kidneys; the outer layer of the adrenal glands releases cortisol and corticosteroids and the inner layer releases catecholamines (noradrenaline, adrenaline). These hormones are our stress response hormones. For those with Persistent CRPS, the overactive firing of the sympathetic nervous system can lead to autonomic exhaustion. In extreme cases, this can lead to Adrenal Insufficiency/Addison’s disease. While short-term courses of corticosteroids can be assistive, particularly close to onset, long-term use of steroids to boost the immune system is generally not recommended to treat CRPS.^278,279,280 However, in circumstances of Adrenal Insufficiency, using corticosteroids or adrenocorticotropic hormones to get the body to a functional level may be necessary. 

The second feedback loop that is likely most recognizable is the HPG axis, which runs to the gonads, either the ovaries or testes respectively. For more details, see the Reproductive section.

The third feedback loop one is most likely to recognize is the HPT axis, which runs to the thyroid gland.²⁸¹ This can lead to hypothyroidism or hyperthyroidism, depending on the individual. There are medications that can address both an underactive or an overactive thyroid. If having issues with the thyroid, based on its activity, one may have issues with sweating, weight, heat/cold intolerance, nail problems, stool issues, nervousness/anxiety or depression/irritability, heart rate, puffiness in the face, muscle pain or weakness, hair loss and breakage, fatigue, and sleep difficulties, among other symptoms.  

Some practical tips and tricks:

• Stimming, or self-stimulating behavior, is repetitive actions that help regulate and soothe a hyper- or hypo-active nervous system. All people stim to varying degrees, though this is most often associated with neurodivergent individuals. When experiencing a CRPS-induced panic attack (or what I personally call a ‘sympathetic strike’), tapping a 1 2 3&4 rhythm over your sternum—in any position, either while rocking or not, in time with music with a 4/4 beat or not—can help calm the body and bring a person back to a more tolerable baseline. If this approach works for you, you might also find this 1 2 3&4 method applicable while not experiencing a sympathetic strike and over a broader range of the body, such a shoulders, inner elbows, palms/wrists, hips, and soles of the feet to train the body that once this modality starts being utilized it is time to start calming down. It is best paired with diaphragmatic breathing and other stress management techniques as well.
• If on long-term mineral corticosteroids like fludrocortisone for adrenal insufficiency, there can be a range of side effects, including some more severe ones that can negatively overlap with CRPS fairly severely. Those taking this medication should monitor any changes they notice and stay up to date on their labs, particularly if they are at higher doses and with chronic, long-term use.^{282,283,284,285}

Eyes & Ears: Vision and Hearing

Some people with CRPS may develop complications with the eyes or ears. Some researchers think this may be a result of either inhibited circulation, CRPS-induced white matter density changes in the brain, the dysfunctional autonomic nervous system at the level of the brainstem, or a combination.

In the eyes, CRPS patients may experience blurred or double vision, trouble focusing, light sensitivity, dry eyes, or excessive tear secretion.²⁸⁶ Light sensitivity is known as photophobia, and it is greater on the CRPS-affected side in tested patients as well as having a lower discomfort brightness threshold than those without CRPS; headaches were also more likely to occur on the CRPS-affected side.²⁸⁷ High contrast images, non-natural geometric shapes, visual conflict, simulation of illusory movement, and ambiguous reversible images can also worsen pain, indicating a heightened sensitivity to an array of visual stimuli.²⁸⁸

If the ocular nerve joins other nerves in a neuropathic pain state,^289,290 the individual may experience a stabbing or burning pain that radiates into their brain like an ice pick or a railroad tie being shoved through their eye socket. Another small study indicates that those with CRPS are at increased risk for immune-related eye disease; patients with conditions that restrict blood flow to the small blood vessels are also at an increased risk for developing scleritis, an inflammatory condition of the white of the eye.²⁹¹ 

Anecdotally, those with CRPS may also notice they develop Visual Snow Syndrome (or that it becomes more prominent if they had it prior to their CRPS onset). VSS is a neurological condition where tiny dots fill the visual field, often described as looking like old TV static, with other symptoms including photophobia, entoptic phenomena (visual effects originating within the eye), palinopsia (prolongation of afterimages) and nyctalopia (poor vision in low light).^292,293,294

In the ears, those with CRPS may experience tinnitus (a ringing, buzzing, whirring, or piercing sound in the ears), bouts of dizziness, sensitivity to certain sounds, and pain associated with sound.²⁹⁵ Research indicates that this pain related to sound is not due to damage to the inner ear, but instead due to auditory processing in the brainstem and midbrain.²⁹⁶ After a startling noise, those with CRPS report both an increase in pain and auditory discomfort.²⁹⁷ This pain from sound (also known as hyperacusis) appears to be common in those with severe cases, particularly those who also experience dystonia, and may indicate another manifestation of central sensitization in this complex condition.²⁹⁸ The primary researcher referenced for this section on hearing is of the view that what he has learned of how CRPS impacts hearing, particularly where it comes to hyperacusis, indicates that the brain region primarily responsible for controlling the sympathetic nervous system, the locus coeruleus, could be involved in this symptom.²⁹⁹

Some practical tips and tricks:

• Blue light filter glasses/lenses or blue light filter apps like Twilight, F/lux, Color Veil, and Eye Comfort Shield can help reduce light sensitivity when looking at your PC or mobile device.
• Adjustable LED lights with handheld remote can have their brightness and color altered without having to get up from where you are sitting, standing, or laying down. Green light appears to reduce some migraine severity, while others seem to have good results with a deep pink/magenta/rose color for light sensitivity.^300,301
• Wearing polarized sunglasses, Transitions lenses, and/or hats while in brightly lit environments. During golden hour, amber glasses may be more assistive. 
• If using eye drops for dry eye, ensure they are lubricating eye drops and not for redness. Redness drops cause vasoconstriction and repeated use can be detrimental, particularly for those who are ischemia-dominant. 
• Spend time in nature or give your eyes opportunities to look at natural, unstructured, low contrast, low conflict, unambiguous stimuli that is at least 5 ft away periodically while using screens to reduce eye strain.
• If you can afford it, see your optometrist regularly and wear your glasses if you need them; our eyes are the most sensitive organs in our bodies and often under incredible sensory bombardment and strain. If more complex or rapidly evolving eye issues develop, consider seeing an ophthalmologist or a neuro-ophthalmologist instead as they have much more extensive training and a better understanding of how complex health conditions can affect the eyes, optic nerves, and visual cortex of the brain. 
• Consider the visual mess and how the brain is processing it. Cleaning can be a challenge, but having psychological and visual space may reduce your pain, particularly if you have compulsions around tidiness. It doesn’t have to be clean; just having the space open can alter the visual perception immensely by reducing the amount of stimuli.
• Noise-canceling headphones can help reduce sensory overload or pain from sound.
• There are several brands of ear inserts to help reduce tinnitus; your mileage may vary. 
• Taking time to be silent and have silence can help with coming back to a state of balance or at least increase calm and reduce some pain from the noise of the day, particularly if you have to continue to work, parent, or have errands to run in the public space. 
• Consider all the background noise that may be contributing to your agitation and discomfort: fans, air conditioning, electrical humming, water running, neighborhood noises, and other sounds that you may not be consciously aware of but which your brain is subconsciously processing. Reducing or eliminating some of these sounds for a period of time may assist you. This is particularly relevant for neurodivergent individuals.
• White noise can be helpful for some, but there are other frequencies that may be helpful as well. Pink noise can help with concentration and sleep.³⁰² Brown noise can aid the hypothalamus in memory processing and recall, which for some may result in better focus, concentration, creativity, and stress reduction. Green noise is a newer area of study, but those that benefit from it find it produces a calming feeling; the frequency is in the 500Hz range, and the current hypotheses are that it’s calming from being the frequency humans can register from within the womb.³⁰³  

Migraines: Intense Headaches

People who live with CRPS may develop intense and/or chronic headaches after CRPS comes into their lives. Alternatively, they may have experienced migraines as a part of their pre-CRPS experience that then either continue at the same rate or significantly worsen post-CRPS. 

One study found that migraines may be a risk factor for the development of CRPS as those with CRPS were 3.6 times more likely to have migraines and nearly twice as likely to have chronic daily headaches as the general population.³⁰⁴ Those with CRPS and migraines report earlier onset of CRPS, symptoms are present in more extremities, and deep joint pain is more common than those without migraines.

Increased length of living with CRPS is associated with increased migraine frequency, as well as a higher prevalence of psychological and medical disorders. Both migraines and CRPS can be incredibly debilitating conditions, with migraines independently ranking at a 7 or 8 on the Stanford Comparative Pain Scale,³⁰⁵ depending on the severity; when combined, these two disorders can take someone down for the count or, if they live with chronic daily migraines and the daily pain of CRPS, create a person whose pain scale is so skewed and distorted that it is difficult for them to relate to the general population or for most people to comprehend their daily lived experience—particularly if they see the person with CRPS going about their daily tasks of living with a fairly straight face and not complaining all the time. 

Migraines and CRPS share several underlying factors and have a high association.^{306,307,308,309,310,311} Some researchers are drawing attention to the shared central sensitization pathophysiology and ability for migraines to create body pain and allodynia.^{312,313,314,315}

Another study found that those with CRPS share similar changes to brainstem excitability and the nociceptive blink reflex as those with migraines, which may one day be able to be used as part of a diagnostic biomarker or to follow disease progression.³¹⁶

While the contributions of the vasculature and endothelial cells are under debate in migraines,^{317,318,319,320} it is important to take into consideration the endothelial, vasomotor, neuroinflammatory, and sensitization dysfunction that are primary pillars of CRPS and how that can negatively impact migraine frequency and intensity.

Those with CRPS may also experience increased facial pain in the trigeminal facial nerve, also known as trigeminal neuralgia, another suicide disease. TN might more accurately fall under the CRPS umbrella as CRPS of the face, though those who think CRPS can only affect limbs and cannot spread and therefore cannot affect the head or face would likely strongly disagree with this position. The prevalence of TN ranges from 5.9 to 29.0 per 100,000 person-years;^{321,322,323,324} the prevalence of CRPS ranges from 5.5 to 29.0 per 100,000 person years.^{325,326,327,328}

Some practical tips and tricks:

• Some treatments recommended for chronic migraine are: Botox injections, GCRP-targeting mechanisms, topiramate, and transcranial direct current stimulation^329,330 More research is showing that these treatments for migraines can have benefits for CRPS patients, even those without migraines. Triptans are not recommended for chronic migraines, as they should not be taken more than two to three days per week, and are contraindicated in those with neuropathy, hypertension, and blood flow issues like Raynaud’s; similarly NSAIDs, opioids, and barbiturates are not recommended for chronic migraines due to high prevalence of medication overuse headaches.³³¹
• Green light may be less aggravating during a migraine episode than other colors of light.³³²
• Drink water. Dehydration and water deprivation are associated with triggering headaches and with increased migraine frequency and intensity.^333,334,335
• Keep track of what triggers your migraines. This can be particularly useful for those with chronic daily migraines once you have more effective pain management that reduces your migraine frequency and intensity. Knowing what causes breakthrough migraines can help you avoid or limit your exposure to specific triggers that you already know increase your pain and dysfunction. This one can be quite challenging to do if you have a 24/7 migraine that never goes away though, so it may not be practical for everyone until effective pain management is accessible.

Insomnia: Lack of Sleep

Having trouble getting to sleep, staying asleep, and getting restorative rest are symptoms reported by 80-97% of people living with CRPS.^{336,337,338,339} Half of those individuals who reported interference stated their sleep was disrupted six to seven nights a week and the vast majority of them stating the disruptions to their sleep were substantial. Getting less than seven hours of sleep a night, especially on an extended and/or regular basis, contributes to several other physical and psychological conditions, including stroke and cardiovascular-related health problems, obesity, depression, anxiety, and suicidal ideation.^340,341,342

The reticular formation is the part of the brain responsible for wakefulness. Some researchers think the primary sympathetic control center and area that produces the majority of our noradrenaline, the locus coeruleus, is involved in chronic insomnia, and they have shown hyperactivity of the locus coeruleus in those who struggle with insomnia of longer than three months, which in turn impacts noradrenaline levels and disrupts connections to the area behind the right eye, the orbitofrontal cortex,³⁴³ which is responsible for reward and punishment emotion-based learning, decoding pleasant vs unpleasant sensory input of touch and taste and smell, evaluating relative value in decision making, and limiting impulsive behavior.^344,345,346

This can create a feedback loop of pain creating insomnia and lack of sleep then worsening pain the following day.³⁴⁷

Some practical tips and tricks:

• Newer SNRIs and tricyclic antidepressants can take a multimodal approach, addressing depression, neuropathic pain, insomnia, and anxiety.^348,349,350 SSRIs have also shown to be at least somewhat effective in treating neuropathy.^351,352 If traditional prescription SSRIs are a concern for you, St, John’s Wort is found to be better tolerated and effective as tricycles (and more effective than fluoxetine) as with fewer adverse side effects and low withdrawal symptoms rate;^353,354,355 as with all SSRIs, monitor other drug interactions to prevent Serotonin Syndrome.
• Trazodone, melatonin, and mirtazapine are all drugs recommended as options for CRPS that can help a person get more sleep.³⁵⁶ While benzodiazepines and Z-drugs should definitely be avoided by those with active substance abuse and those using opioids due to respiratory suppression risks, these drugs also have addiction risks and can lead to dependence and tolerance. They are only approved for short term use; if you choose you use benzodiazepines or Z-drugs to help you, keep a close watch for indicators that they might not be a good fit for you.^357,358
• For those with lots of primary sympathetic control hub involvement from the locus coeruleus (indicated by vision and hearing issues or cataplexy), suvorexant/Belsomra and dardidorexant/QVIVIQ are orexin antagonists that are approved for long term use for chronic insomnia.^359,360 Orexin is a neurotransmitter involved in wakefulness and the autonomic nervous system; it is thought that insomnia, sympathetic dysregulation, and excessive orexin neural activity are related.³⁶¹ By blocking the orexin receptor, the excessive activity can be reduced, increasing sleep time and REM.
• White noise or calming music can help decrease sympathetic activity.
• Many with CRPS report an increase in pain during the nighttime hours when activity decreases, distractions are fewer, and spiraling thoughts can amp up sympathetic activity; this phenomena has been often referred to as “painsomnia.” Little movements can increase circulation and reduce pain; mediation or other techniques to help the brain out of rumination thought pathways that increase negative emotional states can be assistive.

Limbic System: Emotional Dysregulation

In earlier sections of this Primer, we discussed in a bit of detail how CRPS uses the “suffering” medial pain pathway that terminates in the limbic system, sending diffuse, motivational, emotionally-charged pain signals, instead of the “sensory” lateral pain pathway that terminates in the cortex, sending discrete, discriminatory, information-oriented pain signals. Due to this medial pathway being the primary tract utilized in CRPS, the quality of pain is quite different to a majority of other kinds of pains and illnesses.

Individuals with CRPS demonstrate neural abnormalities in several areas of the brain associated with emotional and autonomic regulation.³⁶² These affected individuals display impaired emotional decision-making, decreased gray matter density in areas noted in the referenced paper, and both increased and decreased branchings, indicating stronger connections to areas responsible for autonomic and visceral sensory responses and pain tasks and weaker connections in areas responsible for episodic memory, spatial navigation, verbal memory, language processing, attention, and visuospatial memory, coordination of planned motor function, as well as the thalamus and the bridge connecting the two hemispheres of the brain.

Those with CRPS demonstrate decreased perceptual learning, or the ability by which the sensory system responds to stimuli through lived experience.³⁶³ They also show considerable impairment on emotional decision-making tasks, which can affect choices and actions in everyday circumstances where there is emotionally-laden risk.^364,365 Individuals with CRPS are highly prone to develop issues with memory, executive functioning, and emotional dysregulation, particularly anxiety and depression.³⁶⁶ While some studies propose that those with an anxious personality have a higher risk for developing CRPS,³⁶⁷ there is a clear conclusion that CRPS itself creates negative psychological states.³⁶⁸ While there is some controversy within the field, most research does not reveal support for a clear causative “Sudeck’s personality”,^369,370 though there is evidence that children with CRPS have experienced more stressful life events than children with other chronic conditions.³⁷¹

Going through daily life with CRPS is, in and of itself, traumatic; however, for those who also have additional traumatic events they have experienced, the emotional dysregulation CRPS causes can create a situation with a hair-trigger temper and lots of stored emotional energy waiting to explode. Unprocessed traumatic events are memories sitting in the limbic system somewhat like shattered glass, cutting us up as we use our emotional processing centers. Those with many unprocessed traumatic events have a lot of broken glass laying in their brain that needs to be cleaned up by processing those memories and stored bodily trauma, so that the brain can put the information in its appropriate location (like a filing cabinet or a book shelf instead of the floor) now that we have the mental resources to handle it when we didn’t before.  

If we don’t process these memories, they instead sit like bombs inside our bodies, waiting for a triggering event which pulls us back in time and unleashes all that emotional energy we have stored at whatever triggered the association (or if we can contain ourselves for a bit, transferring that energy to something less threatening, which could be positive or very harmful, depending on the context). This process is what is meant in the literal sense in the mental health field when the term “triggered” is used; it also has other terms “amygdala hijack” and “flipping your lid.”^372,373 A person can still experience an amygdala hijack even after they have processed their trauma (after all, the body remembers), but the results will not be nearly as explosive or out of control. 

Amygdala hijacking or flipping one’s lid happens when your sympathetic nervous system is overwhelmed and you can no longer self-comfort or self-soothe.^{374,375,376,377} There is a threat and your body automatically prepares for survival. The alarm bell—the amygdala—sends out danger signals, and the thinking brain—the prefrontal cortex—disconnects; the lid flips, and we become more hostile, more aggressive, less rational, more emotionally driven, and more fear-based. This is all done to protect ourselves, to keep us safe from something our brain registers as dangerous and threatening to our continued well-being. To the traumatized brain, time isn’t linear or even really relevant; during a triggering event, the brain is thrust back to the original context that caused the wounding, even if we do not consciously remember it. This can cause us to act in ways that we later, after we are no longer in that hijacked state, might recognize were a disproportionate reaction to what was happening in the present.

CRPS brains show increased gray matter volume in the areas of the hippocampus and the amygdala thought to be associated with heightened pain expectancy and pain anticipation, places broadly responsible for reward processing and emotional intensity encoding; these two areas have been under particular study for PTSD in war veterans. The length and intensity of CRPS pain is associated with structural abnormalities in the limbic system, gray matter atrophy in the dorsolateral prefrontal cortex, and the increased size in the amygdala and hippocampus.³⁷⁸

This study on The Brain in Chronic CRPS Pain: Abnormal Gray-White Matter Interactions in Emotional and Autonomic Regions is rather dense, but it is excellent.³⁷⁹ In this long excerpt, it states:

“CRPS patients are presumed to be in a constant negative emotional state and exhibit multiple signs of abnormal autonomic function, atrophy of right [anterior insula] in CRPS corroborates the above studies and suggests that central anatomical abnormalities may explain fundamental symptoms of CRPS. . .

“Atrophy in the right [ventromedial prefrontal cortex] was correlated with the interaction of duration and intensity of CRPS pain, which functionally segregates the atrophy in this region from right [anterior insula] and suggests a more global impact, or “emotional load,” of CRPS on the [ventromedial prefrontal cortex]. Atrophy within this region was our primary hypothesis because CRPS patients perform poorly on the emotional decision-making task, which has been shown to critically depend on an intact [ventromedial prefrontal cortex]. In fact, even when CRPS pain is transiently reduced, performance on this task does not improve and CRPS patients do not show evidence of learning the task. . . 

“Emotional decision-making critically depends on the ability to evaluate options in terms of potential reward or punishment; such decisions require proper capturing and evaluation of sensory cues, including bodily autonomic responses. It is thus not surprising that autonomic regulation and monitoring involve many of the same cortical regions implicated in emotional decision-making, especially [anterior cingulate cortex], [ventromedial prefrontal cortex], and [anterior insula]. Therefore differential atrophy of gray matter and abnormal connectivity of associated white matter tracks involving [anterior cingulate cortex], [ventromedial prefrontal cortex], and [anterior insula] in CRPS, in contrast to atrophy of [dorsolateral prefrontal cortex] in chronic back pain, must underlie their differential responses on emotional decision-making, especially given the fact that CRPS is associated with autonomic abnormalities and chronic back pain is not.

“Neurons within the [ventromedial prefrontal cortex] encode the emotional value of sensory stimuli. Moreover, patients with [ventromedial prefrontal cortex] lesions exhibit diminished emotional responses and social emotions, as well as poorly regulated anger and frustration tolerance. A recent study showed also abnormal utilitarian judgments on moral dilemmas that pit considerations of aggregate welfare against emotionally aversive behaviors. . . 

“Importantly, this region projects to the hypothalamus and brainstem areas that link autonomic bodily processes with emotional responses. It also projects to the periaqueductal gray, thereby modulating spinal cord responses to nociceptive inputs. Therefore, the [ventromedial prefrontal cortex] region together with [anterior insula] may be directly involved in determining characteristics of CRPS pain and associated autonomic abnormalities.”

To summarize those five paragraphs: Due to abnormal function and neural atrophy in several areas of the brain responsible for autonomic, emotional, and executive functions, those with CRPS are expected to be in a perpetual negative emotional state by those who research the neuroanatomy of this condition. The degree of brain atrophy in these areas is related to pain intensity and the length of time a person endures it. Emotional decision-making is often severely compromised, and this is thought to be related to impairment of registering, properly processing, and evaluating bodily sensory cues, especially from the autonomic nervous system. This can also cause reduced emotional responses and social emotions (emotions that are brought about by the awareness of another person’s feelings, thoughts, or actions, such as compassion, shame, pride, envy, or elevation), in addition to a shorter temper and lower irritation threshold. Those with damage to the ventromedial prefrontal cortex are also more likely to make utilitarian judgments (what is good/moral is what results in the best outcome for the greatest number of people) in high-conflict personal dilemmas than those without such damage. Autonomic regulation, pain processing centers, emotional apparati, and executive functions are all closely intertwined in CRPS and all quite dysfunctional.

Some practical tips and tricks:

• Mindful awareness and acceptance can help alter our perception of suffering while still being aware of the sensation of pain. It can provide us the space to watch our emotions without getting swept away in them and lashing out.³⁸⁰
• Meditation as an exercise improves activity and efficiency of multiple of the dysfunctional brain areas in CRPS.^{381,382,383,384,385,386,387,388} This style of mental training can be highly assistive for those with CPRS in a wide array of ways.
• Learn how to say, “I do not have the capacity for this right now.” Knowing when we are about to hit our limit and walking away before blowing up can prevent considerable damage to our relationships.
• If we do cause a relationship rupture, learn how to offer genuine apologies and take responsibility for behavior that was our fault.³⁸⁹ 
• However, also remember that apologies are for wrong doing, not wrong being. “I’m sorry for existing [with CRPS].” That is not something to apologize for; you do not need to apologize for existing and taking up space. 
• Special note to parents with children, especially young children: our children learn emotional regulation from us. They watch us model it and learn how to repair after a relationship rupture from us too. For the sake of the child’s healthy individual development and their relationship with you, it is extra important that you learn to manage your emotional disability as best you can. Yes, you will struggle here, and considerably more than most other parents and it isn’t your fault; it is your responsibility to manage for as much harm reduction as possible. Children should not be afraid of their parents, but let’s be honest, parents can be scary, and severe health conditions that leave our parents debilitated, afraid, and in pain can also be terrifying and disorienting to our sense of stability. 
• Don’t rush emotional decision-making. Give yourself plenty of time to consider your options. If you have trusted people to bounce ideas off of, consider getting their perspective before settling on a final decision. 
• Pursue therapeutic options to process traumatic events for more even-keeled emotional processing.

Cortex: Higher Cognitive Functions

While we have covered many of the physical aspects of CRPS in this Primer, some of the symptoms that are not often associated with CRPS often enough in literature but carry some of the most devastating consequences for those who live with the condition are the psychological and cognitive challenges that CRPS brings about through both functional and structural changes to the central nervous system. People can feel like they are going insane, losing their minds, developing dementia, or other severe mental health or neurological conditions that greatly impact one’s ability to function independently in the world. This can be further compounded and traumatizing when the person is disbelieved, delegitimized, or treated like a liar or someone exaggerating for attention. These debilitating symptoms are often reduced to a simple and, in my opinion, inadequate term: brain fog.

  CRPS creates a dysexecutive syndrome (somewhat similar to ADHD), that can negatively impact executive control, word retrieval and verbal fluency, and working memory and remembering facts and access to memories of past events (declarative memory); “significant neuropsychological deficits are present in 65% of patients, with many patients presenting with elements of a dysexecutive syndrome and some patients presenting with global cognitive impairment.”³⁹⁰ 

Those with CRPS display significant prefrontal cortex thinning in the right dorsolateral prefrontal cortex (responsible for attention, emotional judgment, task switching, planning, problem solving, working memory, and novelty-seeking)^391,392 and the left ventromedial prefrontal cortex (responsible for reward and value-based decision making, regulation of negative emotions, and multiple avenues of social cognition).^393,394 These findings may contribute to or explain the executive dysfunction and disinhibited pain perception in CRPS.³⁹⁵

Increased anxiety and poor memory are regular symptoms that are often brought up as causes of concern, frustration, or sources of dark humor within the CRPS community. These symptoms are not simply the results of hysterical people being dramatic about their disproportionate pain that “can’t really be that bad” and looking for an excuse to get out of tasks or call more attention to themselves. The neuroplastic changes in the central nervous system to the amygdala, perirhinal cortex, and hippocampus, in addition to alterations in dendritic structures and neurotransmitter levels can greatly alter memory and emotional balance.³⁹⁶

Additionally, those with persistent CRPS reveal disrupted connectivity and increased blood perfusion in the sensorimotor regions associated with motor planning and control, whereas those in the acute stage showed both reduced gray matter and blood perfusion in areas related to spatial body perception, somatosensory control, and the limbic system.^397,398 

Those with CRPS often have difficulties with body perception, spatial awareness, and recognition of their CRPS-affected limb through a “neglect-like” phenomena often heavily-laden with feelings of intense dislike, disgust, distortion, fear, a feeling of limb deadness, loss of ownership, and other subjective self-perception of the body part linked with disturbed tactile acuity; this is linked with the reorganization of primary and secondary cortical “body schema” maps of the CRPS-affected limb.^{399,400,401,402} They may, despite being able to look down and see that their perception or brain mapping is incorrect, feel that their limb is a different size, shape, or weight, or that it is lacking more parts in their mental landscape than it physically is. Those with CRPS often struggle differentiating left from right limbs, particularly when it comes to their own limbs; this phenomenon seems to be limited to body parts and images of body parts and not a broad spatial lateralization challenge. There are difficulties with precision and accuracy of motor movements of the affected area(s), indicating proprioceptive signaling impairments; when people with CRPS have to rely solely on proprioception without other sensory cues, such as vision, or when the other sensory cues do not align with the proprioception, the CRPS body representation distortions are liable to sharply increase.  

Another study tested parietal lobe functions and revealed that 68% of their small cohort showed at least one deficit and almost 30% failed six or more testing categories, with those with more than one limb affected having a higher incidence rate.⁴⁰³ The testing included recognising objects by touch, identifying fingers of the hand, identifying numbers outlined on the hand, drawing objects, comprehending arithmetic, writing, repeating speech, telling the difference between left and right sides of the body, and intimate gestures or tool use.⁴⁰⁴

Some practical tips and tricks:

• Write things down. Keeping track of things can be difficult. Write down what you need to remember. Keep a calendar. Take notes. Use recipes. Use a calculator. Record phone calls. Use a voice recorder. Do whatever you need to do to organize your mental space.
• Ask a trusted person to help refresh your memory. Not knowing what happened can be scary and it leaves you open for exploitation. Having someone you trust not to take advantage of your poor memory and health condition can make a massive difference. On the other hand, stay alert around untrustworthy people who might leverage your disability to their own advantage at your expense. Voice recordings, notes apps, or a notebook can be useful if you’re alone or do not have a trusted person.
• Slow down. Speeding along or stressing yourself over not being able to speak as fast as you used to or get that word off the tip of your tongue will often just make the situation worse as your sympathetic nervous system increases its activity. Take some deep breaths, slow your system, and give your brain room to think. 
• Do one thing at a time. While many with CRPS may have been extremely competent multi-taskers in the past, if you’re struggling with cognitive dysfunction, do yourself a favor and give your brain an easier time by reducing the load and processing power you’re putting on it at one time. Do things sequentially, and take brain breaks as needed. 
• Explore resources for those with ADHD, including practical tips for daily living to help overcome the motivation activation hump.  
• For those with executive dysfunction difficulties like concentration, focusing, brain fog, or other cognition issues covered in this section, consider discussing these issues with a medical provider who is educated in cognitive and executive function disorders in order to find an appropriate treatment option and testing to help get a more solid idea of what treatment options  are best suited to your individual situation.
• There are apps to work on recognizing left versus right body parts to help the brain begin to retrain itself and begin to counteract the somatosensory cortex reorganization. 
• Ask for accommodations at school or at work under the ADA (or equivalent in your nation). Your doctor may need to fill out a form to help you legally qualify for these protections. 
• Give yourself extra time for tasks that involve executive planning and task switching; find ways to help engage your brain for motivation and reward. 
• Try breaking tasks into set times instead of checklist tasks that you don’t stop until it’s finished. Prioritize what has to happen versus what you want to happen versus what can be delegated out to someone else to accomplish. You don’t have to do it all, and don’t let perfect be the enemy of complete. 
• Break huge tasks into many smaller ones that are easier to manage.
• Set timers or alarms to remind you when things need to be started.
• Proprioceptive signaling also informs circulatory signaling. The more an area is moved, the more blood it needs; the less an area is used, the less blood it needs. To conserve resources, if proprioceptive signals aren’t telling the brain an area is burning through resource stores, vessels constrict; this is why people’s legs fall asleep if they sit still or in odd positions for a long time. Due to the ischemia-reperfusion injury cycles in CRPS, increasing proprioceptive signaling can help both circulation and proper body mapping. Whether that’s using a weighted blanket to help confirm the outline of your body, tracing your skin, gently squeezing up or down your limb, or any other kind of movement that affirms where your body is in space without you having to look to visually verify its location can assist, though this can be challenging for those with severe allodynia.

Spreading: Expanding Autonomic Dysfunction

There is a common misconception—particularly among medical professionals—that CRPS remains limited to one limb only and cannot spread. This is a flatly incorrect and outdated viewpoint, usually founded on a lack of proper, evidence-based education about this condition that aligns with current research and understanding of recent medical literature.  

CRPS can spread in a contiguous way (where the original location of pain gradually enlarges to encompass more area), in a contralateral or mirror-image spread (where symptoms move to the opposite side of the body that is similar in size and location to the original location, such as right foot to left foot), in an ipsilateral spread (moving to a limb that is disconnected from the original area, but is on the same side of the body, such as from right hand to right foot), and in a diagonal spread (such as right leg to left arm).^{405,406,407,408,409} Some patients may end up with generalized or systemic CRPS (which affects their entire bodies); greater than 10% of CRPS patients report generalized CRPS with widespread pain.^410,411 Remember that CRPS has pain as a primary symptom, but at its core is truly a condition of autonomic nervous system dysfunction. While many systemic or generalized CRPS patients may also have widespread, full body sensory dysfunction, it is the dysfunctional central and autonomic nervous systems that are the true indicator and that can also be demonstrated through other Budapest Criteria such as vasomotor, sudomotor, lymphatic, motor, and/or trophic dysfunction.

While a majority of people do keep their CRPS limited to their original area of injury, pain, and dysfunction, it is not an overwhelming majority. Between 30-48% of those with CRPS develop the condition in multiple limbs over time.^412,413,414 Some research has over 80% of patients reporting contiguous spread enlarging the original area of pain and dysfunction.⁴¹⁵ When CRPS spreads without an injury, this is called spontaneous spread. 

A traumatic injury preceded spread to a separate limb only between 37-44% of the time for opposite-sided and same-sided limb spread, but over 90% of the time for diagonal spread (which was generally a rare type of spread overall, occurring at a rate of 14%).⁴¹⁶ Spread is associated with those who were younger when they first developed their CRPS and those with more severely affected characteristics and symptoms. 

There is also the tangential issue of recurrent CRPS or relapsing after a period of full or partial remission. This seems more often to occur in those who initially started with “cold” ischemia-dominant type CRPS, but can happen to “hot” reperfusion-dominant types as well.⁴¹⁷ While these recurrent cases are less common, they are also less visible and more difficult to recognise externally. Even when people go into remission, precautions should be taken and lifestyle changes should be maintained to prevent leaving remission at a later date. 

Unfortunately there is no surefire way to guarantee permanent and complete remission of CRPS. An unexpected injury, planned surgery, overtaxing illness, traumatic event, or extended period of emotional, physical, or psychological stress that overstrains our sympathetic nervous system can cause a resurgence of our CRPS, worsening of localized symptoms, or a spread of the condition.⁴¹⁸ If we are lucky, it may just be a short flare that comes and goes; if we are not lucky, our CRPS may be here to join us in our daily lives in its new manifestation in a long-term sort of way. While we are in full or partial remission, steps can be taken to help keep our nervous system in a more appropriate homeostatic balance and give our sympathetic nervous systems a rest.

Some practical tips and tricks:

• CRPS is stress-driven and many people find their spread occurs during times in their lives of high stress, regardless of whether or not they receive an injury. Stress management tools and techniques are helpful for all people, but they are particularly important for those with CRPS to mitigate symptoms and increase quality of life. 
• Three modalities most likely to cause spreading of CRPS are: immobilization, icing/freezing temperatures, and surgery or injury. If you get an injury that requires a cast or brace, something removable (like an Aircast) is a far safer choice than a plaster cast; this will allow you to take it off at least a few times a day to improve circulation to the injured area and disrupt disuse-driven ischemia. Ice and temperature contrast therapy should NOT be done on CRPS patients; if you need something cool, try to keep it above 60°F/15°C—when you go lower than this, the large nerves that are generally working properly stop conducting, leaving only dysfunctional nerves sending signals to the brain. Surgeries should be carefully considered and, if undergone, ketamine used as the anesthetic and sympathetic nerve blocks utilized, if they are still effective for you, to help prevent spread.^{419,420,421,422,423,424,425,426,427} Vitamin C before and after the surgery has been found to reduce the chances of developing CRPS.^{428,429,430,431}
• The sympathetic nervous system innervates bilaterally—or through both sides of the body.⁴³² Due to the nature of this nervous system, treatments from other sections (particularly things like lymphatic drainage/massage) should be done to both sides of the body, even if you are only showing symptoms on one side. 
• Stressing about debilitating pain spreading to other areas can be an easy thing to do, but it is in our best interest to process our feelings as best we can without ruminating or hyperfocusing on it. We can take steps to mitigate spread and damage and that is in our control and something we should definitely do as a responsible approach to health and wellness and our own best interest. However, whether or not our CRPS will spread is not in our control, and obsessing over it and stressing our mind and body out over it will work against us.

Dissociation: Automatic Defense Mechanism of Detachment and Distance

What about when we cannot give our sympathetic nervous system a break and it just keeps firing excessively? Pedal to the metal, flooring the accelerator all the time? We cannot live that way constantly; we’ll destroy ourselves and burn to pieces. So what does the body do?

Here the dorsal vagal parasympathetic nervous system at the base of the spine acts like hard brakes and clamps down on the activity of the revving sympathetic engine. This brake does not stop the sympathetic activity, but rather mutes and dampens it a bit—low flames instead of a roaring bonfire and smoldering embers instead of a roasting pit. This dual sympathetic-dorsal vagal activity is known as dissociation, and it allows us to continue to soldier on when intolerable things are happening to us by creating distance from our bodies, our memories, our environment, and our present moment. 

When dealing the excruciating pain of CRPS that ranks at the top of the McGill pain scale, coming in at  42-47 out of 50 above cancer, childbirth, kidney stones, and unanesthetized amputation of a digit, many people with CRPS can struggle with suicidal ideation and a significant percentage may attempt to act on those urges or actually end their lives and their suffering.⁴³³ 

For those who do not, a common protection mechanism is dissociation. This is not something an individual chooses to do; it is an automatic, unconscious, base self-protection measure the brainstem utilizes to raise our pain thresholds, conserve our energy, and detach us from the traumatic events we are experiencing. The distancing “neglect-like” body distortion phenomenon described in the Cortex section incorporates a kind of depersonalization dissociation.

Dissociation is not a first-line response; it is a coping mechanism to repeated trauma where one feels powerless and without agency. If it has become a first-line response, the individual has lived through some sad and devastating events where they did not receive social support, were unable to escape, and could not fight back in a way that would end in their success. Dissociation occurs when we have first expended our other options (friends, flight, fight, fawn, then freeze). The mental calculations for rotating through threat responses can happen very quickly; the brain is a pattern recognition machine. If we learned through witnessing or experience that shutting down until the threat has passed is our safest option, something has gone terribly wrong in our lives. While dissociation can be a strength to get us through a short-term period of immense stress and harm, living in a dissociated state perpetually or in a chronic, intermittent way is a clear signal that we are well past our limits and into the Distress Zone. If we stay there too long, we will overload, burn out, and break down. 

There are several kinds of dissociation,⁴³⁴ including: depersonalization, where your body feels less real; derealization, where your surroundings seem less real; dissociative amnesia, where you forget substantial information that is not caused by a medical condition; finally there are the more complex dissociative disorders that fall under the Structural Dissociation Model umbrella, such as PTSD, cPTSD, BPD/EUPD , OSDD, and DID.

From an outside perspective, the individual may appear to have “spaced out” or “zoned out” when they’re dissociating. They may stare off into the distance; if you have heard of the “thousand yard stare,” this is also dissociation.⁴³⁵ Their facial expressions and body language may become rigid, muted, and frozen. Their tone of voice may become flatter, harder, quieter, and more monosyllabic, if they can even speak at all. They may appear like they are ignoring you. They may have no or spotty memory of events that took place. When you notice these things, do not be harsh, force the person to look you in the eyes, or demand they speak to you. 

Dissociation happens when a person feels threatened and without alternative effective defense; making them feel more scared, threatened, or on guard will further ingrain the dissociative response. If your goal is to bring them out of that state, harsh, aggressive behavior is counterproductive. The person needs to feel supported, seen, heard, and accepted for who they are as a person, even if you do not approve of or agree with the behavior that brought about this self-protective episode. 

From an internal perspective, things may become more blurry, fuzzy, distant, wooden, mechanical, dreamlike, or as if you are underwater. You may become considerably more detached from your body and your sensation of pain; you may feel like a head controlling a doll’s body or a little person in your brain piloting a mech suit. Your memories may be impacted. On the other hand, you might slip into a headspace where things become crystal clear and sharp and everything is extremely calm; your heart rate slows and your panic attack stops in its tracks; everything is suddenly fine and you are in complete control without those pesky emotions there to disrupt your laser-like focus on the problem at hand. There is a wide array of dissociative possibilities that will vary from person to person and the scale of dissociation is broad, ranging from daydreaming and imaginative play to Complex Post Traumatic Stress Disorder, Borderline/Emotionally Unstable PD, OSDD, and Dissociative Identity Disorder.^{436,437,438,439,440} 

For those in the secondary and tertiary areas of the Structural Dissociation Model (which anyone with cPTSD would fall into one of these two categories; BPD, OSDD, and DID also are in these more complex divisions), getting familiar with Emotional/Traumatized Parts and Apparently Normal/Daily Living Parts can be a very helpful framework to help better understand psychological processes.^441,442,443 These individuals will have more specific “parts” that are responsible for tasks of daily living and parts that hold emotional responses to trauma, such as Fight!, Freeze!, Flee!, Submit!, and Attach! When that person gets triggered (in the amygdala-hijacked, flipped-their-lid sort of way), these emotional parts can come into the forefront and direct the person’s thoughts and behaviors. Depending on the person’s internal cooperation and integration levels, what happens in the aftermath of the triggering event can vary greatly. 

Those with Insecure Attachment Styles, particularly Disorganized/Fearful-Avoidant Attachment, are more prone to dissociation, more likely to experience autonomic and emotional dysregulation, and more likely to have atypical stress responses.^{444,445,446,447,448,449,450,451,452} Thankfully, insecure attachments can, with deliberate effort and the correct conditions, become earned secure attachment that stabilize autonomic reactivity and increase resilience and internal coherence.^{453,454,455,456,457} If you are someone with an insecure attachment style, putting in the work to earn a secure attachment style can greatly assist in reducing sympathetic activity and healthy connection to self and others.

If you or someone you know, love, or treat deals with dissociation, NetCE offers a free course on the fundamentals of Demystifying Dissociation: Principles, Best Practices, and Clinical Approaches.⁴⁵⁸ There are also a great many mental health professionals on YouTube that offer deeper dives into the Structural Dissociation Model and the associated mental health conditions in the primary, secondary, and tertiary divisions.

Some practical tips and tricks:

• A lot of stimuli processing happens below our conscious awareness on an autonomic level. While we may not notice it, our nervous system is still being bombarded with it. Highly stimulating public places may cause dissociative episodes, even if there was no triggering event, simply due to the sheer amount of processing the nervous system is doing that sends the system into overload and then shutdown. 
• Similarly, car rides or other vibrations, certain sights, sounds, smells, or other specific stimuli may be triggers for overload and then shutdown without any specific emotional component due to the autonomic processing of threat analysis.
• Dissociation is not a choice; it’s an automatic defense mechanism to trauma when we are powerless and without options. Don’t blame someone for dissociating.
• While someone is dissociating, they are more vulnerable, especially if they are out in public. If they are in a safe place (at home, a friend’s house, and the like), they may want to be left alone to calm down, regulate, and feel secure. However, if they “zone out” in a public place, leaving them alone can be dangerous, especially if you are on the move and they have mobility difficulties. 
• If we’ve become very used to dissociating, this can become our default response. Is our automatic presumption that we have no other options correct? Is it true that no one will help us? Can we really not leave? Can we not actually defend ourselves? Do we genuinely have no choice but to shut down and numb ourselves to bear the pain as best we can until it’s over? Maybe that’s true and dissociation is our safest solution, but are we 100% sure? Double check before we check out.
• Do you have Emotional Parts and Apparently Normal Parts? Are you aware of them? Do you know when you’re switching between them and who is driving? 
• We are always responsible for our actions—always. Our behavior is our responsibility, and our emotional and psychological disability of CRPS is a reason for our behavior, but it is not an excuse. We can give ourselves grace (and hopefully be treated with grace and compassion by others), but this is not an invitation to treat people poorly just because we are not feeling well. If we lash out, we should take steps to repair the relationship rupture we caused. This is particularly true for parents with young children, both for the sake of your relationship with your child and their individual development. 
• If you deal with complex dissociation, part of acting responsibly is building internal cooperation and increasing integration, so that communication in your system can improve. 
• Responsibility is response ability, and that starts with being able to communicate with yourself and grows from there. 
• Find a safe space to decompress, stabilize, and come back to center.
• Self-soothe and provide yourself comfort, whether that’s through a favorite food, a song that speaks to you, a soft/warm/heavy blanket or jacket, stimming, or a sentimental plushie, whatever helps you re-regulate your nervous system and re-engage with the world, though it is best if we avoid self-soothing behaviors that are also harmful to us.
• Now not everyone will be at this point in their journey or have the needed social structures, but if you have a safe person, a secure social connection with someone who sees, accepts, protects, and supports you, seek that person out when you’re ready or ask them/have a signal for them to come to you. 
• A therapist with training in dissociation may be beneficial and/or necessary depending on the level of dissociation you experience; someone with Internal Family Systems frameworks may be especially assistive.
• Grounding exercises can help us come back into our bodies. Wiggle toes. Clench fingers. Roll your tongue behind your lips and cheeks to loosen up your facial muscles. Roll your head to loosen your neck. When the dorsal vagal activates, the ventral vagal (social connection that controls our facial expressions and is located in our neck) goes offline; stimulating the nerves in the neck and face can help the ventral vagal parasympathetic nerves be more active again. 5 things you see. 4 things you hear. 3 things you feel. 2 things you smell. 1 thing you taste. Use your senses to become presently grounded in what’s happening to you and around you right now. 
• Move slowly and don’t rush yourself; dissociation is a life-threat response. Learn to recognize and acknowledge your terror. Pretending you aren’t afraid when you are is counterproductive and a lie. Don’t lie to yourself. 
• Build trust with yourself and with others who have shown consistently they have your best interest at the forefront in their interactions with you and that they are not exploiting you or taking advantage of your relationship. 
• Seek empathy. This can be difficult, as many who use dissociation as a primary threat response have not received much empathy in their lives, and seeking it out only to be denied it can be retraumatizing. However, if you have found a person you trust who has shown you through consistent action that they value you and will prioritize your well-being, it can be highly restorative to be shown empathy after a time of deep fear. 
• As communication within the self improves, the individual’s fragmented identity can become more organized and feeling can increase exponentially.
• Integrate anger, instead of acting out or acting in; dissociation happens after anger is suppressed. Healthy anger is an expression of boundary violation and it is a primary function of the sympathetic nervous system, meant to keep out that which is harmful and detrimental to us. Learn how to express healthy anger and hold healthy boundaries. 
• Boundaries make clear what is our responsibility (and what isn’t) and what is in our control (and what isn’t). Boundaries are not rules for someone else to follow; their purpose is not to change or control other people. Boundaries are self-imposed limits of acceptable treatment and how we will react when those limits are crossed. Boundaries are not about the other parties’ understanding or compliance; they choose their actions, and we choose if we subject ourselves to further involvement. Over time, boundaries may change, and that’s okay; people grow, and what used to fit in the past can become uncomfortable. Those changes need to be communicated so that everyone can be treated respectfully. 
• Dissociation is a survival technique; be kind, compassionate, and gentle with yourself.

Additional Reading

If you would like to further explore topics brushed upon in this CRPS Primer that are not strictly CRPS-related, here is a curated reading list of various topics from experts in their respective fields, ranging from mental health, neurobiology, interpersonal relationships, attachment, and supportive learning. Many of the topics addressed in these books are quite heavy and, if possible, individuals struggling with these issues would likely benefit from an informed and compassionate professional to assist you in working through them. However, if that is not an option for whatever reason, these resources are here to help increase awareness and fill the gaps. 

Many of these books can be found at local libraries or digital libraries for free, or thrifted for a reduced rate. I recommend checking your free and low-cost resources before paying full-price. Many of these texts are also available in audiobook format.

• Peter Levine, PhD, developer of the neurobiological approach of Somatic Experiencing has written multiple books, including: Waking the Tiger; Healing Trauma; Healing Trauma: A Pioneering Program for Restoring the Wisdom of Your Body; In an Unspoken Voice: How the Body Releases Trauma and Restores Goodness; Trauma Through a Child’s Eyes: Awakening the Ordinary Miracle of Healing; Infancy Through Adolescence; It Won’t Hurt Forever: Guiding Your Child Through Trauma; Freedom from Pain: Discover Your Body’s Power to Overcome Physical Pain; Sexual Healing: Transforming the Sacred Wound; Trauma and Memory: Brain and Body in a Search for the Living Past: A Practical Guide for Understanding and Working with Traumatic Memory
• Bessel van der Kolk, MD, has researched neuroscience, attachment, trauma, and post-traumatic stress since the 1970s. He authored the bestseller The Body Keeps the Score. 
• Gabor Maté, MD, developer of the Compassionate Inquiry approach to trauma and strong proponent of and worldwide educator for the Biopsychosocial Model has written several bestsellers, including: When the Body Says No: Exploring the Stress-Disease Connection; In the Realm of Hungry Ghosts: Close Encounters with Addiction; The Myth of Normal: Trauma, Illness, and Healing in a Toxic Culture.
• Pat Ogden, PhD, body-oriented psychotherapy, somatic psychology pioneer has written Trauma and the Body: A Sensorimotor Approach to Psychotherapy.
• Daniel Siegel, PhD, is the founding co-director of UCLA’s Mindful Awareness Research Center and Executive Director of the Mindsight Institute; he has written: The Mindful Brain: Reflection and Attunement in the Cultivation of Well-Being; Mindsight: The New Science of Personal Transformation; Pocket Guide to Interpersonal Neurobiology: An Integrative Handbook of the Mind; No-Drama Discipline Workbook: Exercises, Activities, and Practical Strategies to Calm The Chaos and Nurture Developing Minds; The Power of Showing Up: How Parental Presence Shapes Who Our Kids Become and How Their Brains Get Wired; Parenting from the Inside Out: How a Deeper Self-Understanding Can Help You Raise Children Who Thrive; The Whole-Brain Child: 12 Revolutionary Strategies to Nurture Your Child’s Developing Mind; Mind: A Journey to the Heart of Being Human; The Yes Brain: How to Cultivate Courage, Curiosity, and Resilience in Your Child; Aware: The Science and Practice of Presence; The Developing Mind: How Relationships and the Brain Interact to Shape Who We Are; and IntraConnected: Me+We as the Integration of Self, Identity, amd Belonging.
• Jon Kabat-Zinn, PhD, is the developer and founder of mindfulness-based stress reduction (MBSR) at UMass Memorial Health. He has written: Wherever You Go, There You Are; Meditation Is Not What You Think; Falling Awake; The Healing Power of Mindfulness; Mindfulness For All: The Wisdom to Transform the World; Mindfulness Meditation for Pain Relief; Everyday Blessings: The Inner Work of Mindful Parenting; Full Catastrophe Living: Using the Wisdom of Your Body and Mind to Face Stress, Pain, and Illness; Mindfulness: Diverse Perspectives on its Meaning, Origins, and Applications; Mindfulness for Beginners: Reclaiming the Present Moment—And Your Life, among others.
• Laurence Heller, PhD, developed the NeuroAffective Relational Model known as NARM and has written Healing Developmental Trauma: How Early Trauma Affects Self-Regulation, Self-Image, and the Capacity for Relationship.
• Svetlana Masgutova, PhD, developer of the Masgutova Neurosensorimotor Reflex Integration MNRI Method and a lecturer on the Early Intervention Faculty of the Wroclaw Medical Academy has written Post-Trauma Recovery: Gentle, Rapid, and Effective Treatment with Reflex Integration.
• Janina Fisher, PhD, is assistant education director of the Sensorimotor Psychotherapy Institute, an EMDR International Association (EMDRIA) consultant, and a former instructor at the Trauma Center has written Healing the Fragmented Selves of Trauma Survivors Overcoming Internal Self-Alienation.
• Onno van der Hart, PhD, has written several works on structural dissociation, but one of the most important and highly regarded books on the topic is The Haunted Self: Structural Dissociation and the Treatment of Chronic Traumatization.
• Richard Schwartz, PhD, developed the Internal Family Systems psychotherapy model and has written Introduction to Internal Family Systems; No Bad Parts: Healing Trauma and Restoring Wholeness with the Internal Family Systems Model; You Are the One You’ve Been Waiting For: Applying Internal Family Systems to Intimate Relationships.
• Francine Shapiro, PhD, developed the Eye Movement Desensitization & Reprocessing psychotherapy model and has written several books, including: EMDR: The Breakthrough “Eye Movement” Therapy for Overcoming Anxiety, Stress, and Trauma; Eye Movement Desensitization and Reprocessing (EMDR) Therapy: Basic Principles, Protocols, and Procedures; Getting Past Your Past: Take Control of Your Life with Self-Help Techniques from EMDR Therapy.
• Pete Walker, MA MFT, has specialized in treating adults with cPTSD for 35 years. He has written Complex PTSD: From Surviving to Thriving, among other works.
• David Emerson, YACEP and prior social worker, is founder and co-director of the Center for Trauma and Embodiment at the Justice Resource Institute which is dedicated to creating body-first, evidence-based models of care for survivors of complex trauma; he has written Trauma-Sensitive Yoga in Therapy: Bringing the Body into Treatment.
• Kristin Souers, MA LMHC and adjunct professor at Gonzaga University School of Education, has written Fostering Resilient Learners: Strategies for Creating a Trauma-Sensitive Classroom and Relationship, Responsibility, and Regulation: Trauma-Invested Practices for Fostering Resilient Learners.
• John Gottman and Julie Gottman, PysDs, are co-founders of the Gottman Institute; John is Professor Emeritus of Psychology at the University of Washington, Julie is in private practice and has been awarded Washington State Psychologist of the Year. The Gottman’s focus on relationships and marriage and have written multiple books, including: The Seven Principles for Making Marriage Work: A Practical Guide from the Country’s Foremost Relationship Expert; The Relationship Cure: A 5 Step Guide to Strengthening Your Marriage, Family, and Friendships; Why Marriages Succeed or Fail: And How You Can Make Yours Last; Ten Lessons to Transform Your Marriage; The Love Prescription, And Baby Makes Three: The Six-Step Plan for Preserving Marital Intimacy and Rekindling Romance After Baby Arrives; What Makes Love Last?: How to Build Trust and Avoid Betrayal; Couple’s Guide to Communication; The Man’s Guide to Women: Scientifically Proven Secrets from the “Love Lab” About What Women Really Want; The Marriage Clinic: A Scientifically Based Marital Therapy; The Science of Trust: Emotional Attunement for Couples; What Am I Feeling?; When Men Batter Women: New Insights into Ending Abusive Relationships; What Predicts Divorce?: The Relationship Between Marital Processes and Marital Outcomes; and Meta-Emotion: How Families Communicate.
• Lindsay Gibson, PsyD, has written Adult Children of Emotionally Immature Parents: How to Heal from Distant, Rejecting, or Self-Involved Parents.
• Stephanie Kriesberg, PsyD, has written Adult Daughters of Narcissistic Mothers: Quiet the Critical Voice in Your Head, Heal Self-Doubt, and Live the Life You Deserve.
• Ramani Durvasula, PhD, better known by her YouTube channel handle Dr. Ramani, is a renowned expert on narcissism and entitled, difficult people, providing education on how to deal with these kinds of individuals and set boundaries and has written several books, including: Should I Stay or Should I Go: Surviving a Relationship with a Narcissist; Don’t You Know Who I Am?: How to Stay Sane in an Era of Narcissism, Entitlement, and Incivility; It’s Not You: Identifying and Healing from Narcissistic People.
• Les Carter, PhD, is another expert on high control, low empathy, manipulative behaviors, and an attitude of entitlement; he is perhaps better known for his YouTube channel Surviving Narcissism. He has written several books, including: Enough about You, Let’s Talk about Me: How to Recognize and Manage the Narcissists in Your Life; When Pleasing You Is Killing Me: Volume 1; People Pleasers: Helping Others Without Hurting Yourself; Imperative People: Those Who Must Be in Control—How to Keep Your Greatest Strength From Becoming Your Greatest Weakness; Distant Partner: How to Tear Down Emotional Walls and Communicate with Your Husband; Getting the Best of Your Anger; Good ‘n’ Angry; The Anger Trap: Free Yourself from the Frustrations That Sabotage Your Life. [Disclosure: This man is a Christian and that does appear to influence his writing in at least some of his works, though it does not bleed through in his YouTube channel that I have noticed.]

Closing: Final Thoughts

Complex Regional Pain Syndrome is a dynamic, multifaceted condition. Both nicknames, “the suicide disease” and “the great imitator,” are well-deserved and speak to the complexities and broad, intense impacts this disorder can have on those affected and their loved ones.

Now not everyone diagnosed with CRPS will experience every symptom discussed in this Primer, and this Primer likely did not cover every possible manifestation and complication of this condition. However, hopefully it provided a solid overview of what CRPS looks like in a practical way, as well as basic explanations of how the dysfunction is taking place in the body and some mitigating actions that can be taken to improve one’s quality of life.

Living with CRPS requires immense strength of will. The internal drive necessary to carry on with this condition is enormous. In my time in this community, I have noticed that CRPS seems to disproportionately impact those who could be readily classified as overachievers, ambitious, Type A, highly motivated, and adrenaline junkies. While many barbs that those with CRPS receive from people who don’t understand what our condition entails often include “lazy,” “a burden,” “unmotivated,” “wasted potential,” or other similar phrases that have a tendency to cut to the core of high achievers’ deep fears about sense of self, in reality our ambition and motivation often grows exponentially; it is just that everything requires exponentially more effort. 

If you have CRPS, I see the effort, determination, and dedication you’re exerting, and I understand how much it can take out of a person. You’re doing a good job, and you deserve compassion and aid. 

I’d like to wrap up this Primer with two quotes from the pain management specialist who diagnosed me; these statements helped shift my perspective, one when I was coming to terms with my new reality and feeling very much like both a burden and a failure and the other after I started making some improvements. Perhaps they can help some of you readers as well.

“When living with CRPS, every day above ground is a victory.”

“Discipline is important, now more than ever. Just because you feel better doesn’t mean you are better.”

Living and thriving with CRPS often requires some serious reframing of how we view the world and how we view ourselves and our relationships. Grieving who we thought we’d be and the plans we had for our future can be a slow, painful process. This disorder has the depressing tendency to put in stark clarity, as it reduces our capabilities and capacities, who is around you because you are useful and they like what you can do for them and who is around you because they enjoy you as a person without having to earn attention through action. Learning how to live with joy and hope while still being in excruciating pain is a challenging task that requires moment to moment mindful awareness and acceptance, particularly since CRPS runs on the “suffering” medial pain pathway. 

Maintaining discipline with treatment regimens, especially once making improvements or having achieved partial remission, is important to keep the forward momentum and trajectory. Many people who reached full remission were not told that it is possible to relapse and pushed their bodies too hard, experiencing another injury or undue stress that they could have otherwise avoided and having their CRPS rear its head again. 

Particularly for those who have persistent CRPS, management is a lifestyle with four primary pillars: psychological, neurological, physiological, and dietary modalities. It is not a short, several month stint of aggressive treatment and then life goes back to just the way it was before; even if full remission or complete resolution of CRPS is achieved, but especially for those cases that are severe or long-standing, appropriate therapeutic treatment includes lifestyle changes that last an entire lifetime for happier, healthier, less stressful, more integrated living.

Many in the CRPS-sphere use a “warrior” mentality and often talk about “fighting against” their CRPS. While I very much understand why they hold that perspective as CRPS can feel like the ultimate bodily betrayal of sense of self and why people would want to battle it to death as an enemy, that is not an approach or model I will use in my work, and if you elect to consume more of my content, that is not a framework you will find me utilizing. The closest analogy you will find in my work is “fighting with” as an unlikely ally rather than a mortal foe and the “warrior monk” archetype instead of the “crusader warrior” with swords and shields that seems to dominate many chronic health circles and which is particularly identified with in the CRPS community. Many of you with CRPS may disagree with me, and that’s okay, but that is my personal position.

Rather, I will approach CRPS as a feral, abused dog, lashing out at us in rage and pain—one which needs our aid, our support, and our protection to feel safe and heal. CRPS is the dysfunction of our own autonomic nervous systems and I will not advocate going to war against ourselves when instead we could become our most ardent, most trusted defenders, treating ourselves with compassion, understanding, and loving acceptance.

Life with CRPS is not hopeless nor is it meaningless, though there is a steep learning curve and the fear of the unknown and the social isolation can be significant hurdles to overcome. If I wrote this Primer well, then after reading this you now have more resources to address the unknown. I highly recommend finding a CRPS community, whether in person or online, to be able to see your lived experience reflected back at you and know that you are not alone and that there are others out there who understand what you’re living through; even if you don’t actively participate, being able to see others like you can lift a massive psychological weight.

If you don’t have CRPS and don’t personally know anyone who has it, I hope this Primer provides a comprehensive overview about the systemic effects of a severely misunderstood condition. 

If you’re in healthcare specifically, it is my deep desire that this expands your understanding of the various ways in which CRPS can impact the entire body, that the frequent and extremely psychologically damaging delegitimizing behavior and medical gaslighting that CRPS patients experience on the regular will reduce, and that you will be our advocates. We are an extremely small community, and we are tired. The vast majority of us have at least some level of medical trauma caused by those who are meant to provide us aid and many may struggle to stand up for ourselves when we are being treated poorly by healthcare professionals in authority positions for a variety of reasons; use this knowledge and the resources linked here to speak on our behalf when you see us being treated in ways that are counter to our interests, that go against medical evidence, or that are views of CRPS that are based in ignorance and misinformation. 

If you don’t have CRPS and do personally know someone who has it, I hope this Primer helps you better understand their struggles and expands your empathy for their circumstances. While many with CRPS prefer to be as independent as they can manage and may have difficulties asking for help, some compassion, active listening, and remembering their limitations goes a long way.

If you do have CRPS, I hope this Primer reduces your fear and increases your autonomy. Your life isn’t over. You still have valuable things you can offer. And even if you didn’t, you don’t have to offer something in return to justify your right to exist and dare to take up space. Life isn’t hopeless, and things can get better.

If you are struggling to meet your needs, my next major project, the Resource List, will be linked here when it is completed. Projected finish date is at some point in the first half of 2024.

This concludes the CRPS Primer. If you made it this far, thanks for sticking with me. I hope you learned something, and I hope to see you next time.

Acknowledgement

CRPScontender thanks ThePharmachinist for their time and effort in editing this Primer, for offering several contributions to improve this work in breadth, depth, and accuracy, and for their steadfast encouragement and support.

References

1. Organization of the Nervous System (National Cancer Institute, SEER Training Modules) ↩︎
2. Chudler, divisions of the nervous system (U of Washington, Neuroscience for Kids) ↩︎
3. Kaya, Sarikcioglu, Sir Herbert Seddon (1903–1977) and his classification scheme for peripheral nerve injury (Child’s Nervous System, 2014) ↩︎
4. Bhandari, Management of peripheral nerve injury (Journal of Clinical Orthopaedics and Trauma, 2019) ↩︎
5. Kim, Diagnosis of complex regional pain syndrome (Annals of Clinical Neurology, 2022) ↩︎
6. Misidou, Papagoras, Complex Regional Pain Syndrome: An update (Mediterranean Journal of Rheumatology, 2019) ↩︎
7. Pharm, Bruehl, Complex Regional Pain Syndrome (NORD, 2023) ↩︎
8. Oaklander et al, Evidence of focal small-fiber axonal degeneration in complex regional pain syndrome-I (reflex sympathetic dystrophy) (Pain, 2006) ↩︎
9. Oaklander, Fields, Is reflex sympathetic dystrophy/complex regional pain syndrome type I a small-fiber neuropathy? (Annals of Neurology, 2009) ↩︎
10. Rasmussen et al, Bilaterally Reduced Intraepidermal Nerve Fiber Density in Unilateral CRPS-I (Pain Medicine, 2018) ↩︎
11. Kharkar et al, Skin biopsy in complex regional pain syndrome: case series and literature review (Pain Physician, 2012) ↩︎
12. Fabry et al, Which Method for Diagnosing Small Fiber Neuropathy? (Frontiers in Neurology, 2020) ↩︎
13. Goebel et al, The Valencia consensus-based adaptation of the IASP complex regional pain syndrome diagnostic criteria (PAIN, 2021) ↩︎
14. Bean et al, Extent of recovery in the first 12 months of complex regional pain syndrome type-1: A prospective study (European Journal of Pain, 2015) ↩︎
15. Bean et al, The Outcome of Complex Regional Pain Syndrome Type 1: A Systematic Review (Journal of Pain, 2014) ↩︎
16. Raja et al, Complex Regional Pain Syndrome: A Comprehensive Qualitative Research Study on Unmet Needs in the “Patient Journey” (Journal of Pain Research, 2021) ↩︎
17. Packham et al, Persons with Complex Regional Pain Syndrome Renegotiate Social Roles and Intimacy: A Qualitative Study (Pain Medicine, 2020) ↩︎
18. Beales et al, Exploring peoples’ lived experience of complex regional pain syndrome in Australia: a qualitative study (Scandinavian Journal of Pain, 2021) ↩︎
19. Kelmer, Furnee, The Impact of Chronic Pain on Life in the Household (Journal of Pain and Symptom Management, 2002) ↩︎
20. van Velzen et al, Health-related quality of life in 975 patients with complex regional pain syndrome type 1 (Pain, 2014) ↩︎
21. Antunovich et al, “I Don’t Identify with It”: A Qualitative Analysis of People’s Experiences of Living with Complex Regional Pain Syndrome (Pain Medicine, 2021) ↩︎
22. Johnson et al, Complex regional pain syndrome what is the outcome? – a systematic review of the course and impact of CRPS at 12 months from symptom onset and beyond (European Journal of Pain, 2022) ↩︎
23. Harris et al, An Examination of Leisure and Quality of Life in Individuals with Complex Regional Pain Syndrome (CRPS) (Annual in Therapeutic Recreation, 2016) ↩︎
24. Bharwani et al, Denying the Truth Does Not Change the Facts: A Systematic Analysis of Pseudoscientific Denial of Complex Regional Pain Syndrome (Journal of Pain Research, 2021) ↩︎
25. Wilson et al, Complex Regional Pain Syndrome: What Is the Evidence? (Pain Medicine, 2017) ↩︎
26. Renee et al, Rethinking the Psychogenic Model of Complex Regional Pain Syndrome: Somatoform Disorders and Complex Regional Pain Syndrome (Anesthesiology and Pain Medicine, 2012) ↩︎
27. Oaklander, RSD/CRPS: The end of the beginning (Pain, 2008) ↩︎
28. Beerthuizenl et al, The association between psychological factors and the development of complex regional pain syndrome type 1 (CRPS1) — A prospective multicenter study (European Journal of Pain, 2012) ↩︎
29. Bean et al, Do psychological factors influence recovery from complex regional pain syndrome type 1? A prospective study (Pain, 2015) ↩︎
30. Harden et al, Validation of proposed diagnostic criteria (the “Budapest Criteria”) for Complex Regional Pain Syndrome (Pain, 2010) ↩︎
31. Iolascon et al, Complex regional pain syndrome (CRPS) type I: historical perspective and critical issues (Clinical Cases in Mineral and Bone Metabolism, 2015) ↩︎
32. Kim, Diagnosis of complex regional pain syndrome (Annals of Clinical Neurology, 2022) ↩︎
33. Kim, Diagnosis of complex regional pain syndrome (Annals of Clinical Neurology, 2022) ↩︎
34. Goebel et al, The Valencia consensus-based adaptation of the IASP complex regional pain syndrome diagnostic criteria (Pain, 2021) ↩︎
35. Arcilla, Tadi, Neuroanatomy, Unmyelinated Nerve Fibers (StatPearls, 2023) ↩︎
36. McGill University, Ascending Pain Pathways (The Brain from Top to Bottom) ↩︎
37. Xie et al, Role of sensory C fibers in hypoxia/ reoxygenation-impaired myogenic constriction of cerebral arteries (Neurological Research, 2010) ↩︎
38. Zhang et al, The role of C-afferents in mediating neurogenic vasodilatation in plantar skin after acute sciatic nerve injury in rats (BMC Neuroscience, 2020) ↩︎
39. Coderre, Bennett, A Hypothesis for the Cause of Complex Regional Pain Syndrome – Type I (Reflex Sympathetic Dystrophy): Pain Due to Deep-Tissue Microvascular Pathology (Pain Medicine, 2010) ↩︎
40. Bruehl, Warner, An Update on the Pathophysiology of Complex Regional Pain Syndrome: Altered Cutaneous Innervation after Injury (Anesthesiology, 2010) ↩︎
41. Oaklander et al, Evidence of focal small-fiber axonal degeneration in complex regional pain syndrome-I (Pain, 2006) ↩︎
42. Glatte et al, Architecture of the Cutaneous Autonomic Nervous System (Frontiers in Neurology, 2019) ↩︎
43. Pierau et al, Regulation of Efferent Functions of C-Fiber Nociceptors (Thermotherapy for Neoplasia, Inflammation, and Pain, 2001) ↩︎
44. Porges, The polyvagal theory: New insights into adaptive reactions of the autonomic nervous system (Cleveland Clinic Journal of Medicine, 2009) ↩︎
45. Chu, The Window of Tolerance – A (Very Basic) Introduction to Polyvagal Theory (Intuitive Healing, 2020) ↩︎
46. Center for the Developing Child, Toxic Stress (Harvard University) ↩︎
47. Center for the Developing Child, What are ACEs? (Harvard University) ↩︎
48. Nemeroff, Neurobiological consequences of childhood trauma (Journal of Clinical Psychiatry, 2004) ↩︎
49. Kempke et al, Effects of early childhood trauma on hypothalamic–pituitary–adrenal (HPA) axis function in patients with Chronic Fatigue Syndrome (Psychoneuroendocrinology, 2015) ↩︎
50. Davies, Flipping your Lid & Widening your Window of Tolerance (Vitality Collective, 2021) ↩︎
51. Missimer, How to Map Your Own Nervous System: The Polyvagal Theory (Movement Paradigm, 2020) ↩︎
52. McGill University, The Pleasure Centers (The Brain from Top to Bottom) ↩︎
53. Moseley, Graded motor imagery is effective for long-standing complex regional pain syndrome: a randomised controlled trial (Pain, 2004) ↩︎
54. Mendez-Rebolledo et al, Update on the effects of graded motor imagery and mirror therapy on complex regional pain syndrome type 1: A systematic review (Journal of Back and Musculoskeletal Rehabilitation, 2017) ↩︎
55. Johnson et al, Using graded motor imagery for complex regional pain syndrome in clinical practice: Failure to improve pain (European Journal of Pain, 2011) ↩︎
56. Strauss et al, Graded motor imagery modifies movement pain, cortical excitability and sensorimotor function in complex regional pain syndrome (Brain Communications, 2021) ↩︎
57.  Arcos-Holzinger et al, Virtual reality in managing Complex Regional Pain Syndrome (CRPS): a scoping review (Frontiers in Neurology, 2023) ↩︎
58.  Chau et al, Immersive Virtual Reality for Pain Relief in Upper Limb Complex Regional Pain Syndrome: A Pilot Study (Innovations in Clinical Neuroscience, 2020) ↩︎
59. Won et al, Assessing the Feasibility of an Open-Source Virtual Reality Mirror Visual Feedback Module for Complex Regional Pain Syndrome: Pilot Usability Study (Journal of Medical Internet Research, 2021) ↩︎
60. Austin, Siddall, Virtual reality for the treatment of neuropathic pain in people with spinal cord injuries: A scoping review (Journal of Spinal Cord Medicine, 2021) ↩︎
61. Donegan et al, Altered bodily perceptions in chronic neuropathic pain conditions and implications for treatment using immersive virtual reality (Frontiers in Human Neuroscience, 2022) ↩︎
62.  Scientific Background (Svetlana Masgutova Educational Institute, 2023) ↩︎
63. Scientific Articles  (Svetlana Masgutova Educational Institute, 2023) ↩︎
64. Tatarinova et al, The Impact of MNRI Therapy on the Levels of Neurotransmitters Associated with Inflammatory Processes (International Journal of Molecular Sciences, 2020) ↩︎
65. Berg et al, The Masgutova Neurosensorimotor Reflex Integration (MNRI®): A
    Scoping Review (Open Journal of Occupational Therapy, 2022) ↩︎
66. Coppola, Exploring Research Knowledge, Attitude, and Practice of MNRI®
    Core Specialists (Seton Hall University, 2022) ↩︎
67. McCleane, Topical application of doxepin hydrochloride, capsaicin and a combination of both produces analgesia in chronic human neuropathic pain: a randomized, double-blind, placebo-controlled study (British Journal of Clinical Pharmacology, 2000) ↩︎
68. Harden et al, Complex Regional Pain Syndrome: Practical Diagnostic and Treatment Guidelines, 5th Edition (Pain Medicine, 2022) ↩︎
69. McCleane, Topical application of doxepin hydrochloride can reduce the symptoms of complex regional pain syndrome: a case report (Injury, 2002) ↩︎
70. Zhao et al, The Effect of Ketamine Infusion in the Treatment of Complex Regional Pain Syndrome: a Systemic Review and Meta-analysis (Current Pain and Headache Reports, 2018) ↩︎
71. Chitneni et al, Use of Ketamine Infusions for Treatment of Complex Regional Pain Syndrome: A Systematic Review (Cureus, 2021) ↩︎
72. Connolly et al, A Systematic Review of Ketamine for Complex Regional Pain Syndrome (Pain Medicine, 2015) ↩︎
73.  Kirkpatrick et al, Optimizing the Treatment of CRPS With Ketamine (The Clinical Journal of Pain, 2020) ↩︎
74. Pickering, McCabe, Prolonged ketamine infusion as a therapy for complex regional pain syndrome: synergism with antagonism? (British Journal of Clinical Pharmacology, 2014) ↩︎
75. Xu et al, Intravenous Ketamine Infusion for Complex Regional Pain Syndrome: Survey, Consensus, and a Reference Protocol (Pain Medicine, 2018) ↩︎
76. Azari et al, Efficacy and Safety of Ketamine in Patients with Complex Regional Pain Syndrome: A Systematic Review (CNS Drugs, 2012) ↩︎
77. Loix et al, The anti-inflammatory effects of ketamine: state of the art (Acta Anaesthesiologica Belgica, 2011) ↩︎
78. Schwartzman et al, Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study (Pain, 2009) ↩︎
79. Sigtermans et al, Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1 (Pain, 2009) ↩︎
80. Sigtermans et al, An observational study on the effect of S+-ketamine on chronic pain versus experimental acute pain in Complex Regional Pain Syndrome type 1 patients (European Journal of Pain, 2010) ↩︎
81. Schwartzman et al, Efficacy of 5-Day Continuous Lidocaine Infusion for the Treatment of Refractory Complex Regional Pain Syndrome (Pain Medicine, 2009) ↩︎
82. Su et al, Local subcutaneous lidocaine injection for the treatment of complex regional pain syndrome: a case report and literature review (Frontiers in Neurology, 2023) ↩︎
83. Fallico et al, A randomised placebo-controlled clinical trial on the efficacy of local lidocaine injections and oral citalopram for the treatment of complex regional pain syndrome (Journal of Plastic, Reconstructive & Aesthetic Surgery, 2022) ↩︎
84. Rickard, Kish, Systemic Intravenous Lidocaine for the Treatment of Complex Regional Pain Syndrome: A Case Report and Literature Review (American Journal of Therapeutics, 2016) ↩︎
85. Hoikkanen et al, Long-Term Outcome of Spinal Cord Stimulation in Complex Regional Pain Syndrome (Neurosurgery, 2021) ↩︎
86. Prokopienko, Sobstyl, Spinal cord stimulation for treatment of complex regional pain syndrome: a single-centre retrospective case series study (Polish Journal of Neurology and Neurosurgery, 2022) ↩︎
87. Deer et al, Dorsal root ganglion stimulation yielded higher treatment success rate for complex regional pain syndrome and causalgia at 3 and 12 months: a randomized comparative trial (Pain, 2017) ↩︎
88. Pendem, Jassal, Dorsal Root Ganglion Stimulation as Treatment for Complex Regional Pain Syndrome of the Foot Refractory to Spinal Cord Stimulation: A Case Report (Cureus, 2021) ↩︎
89. D’Souza, Dorsal Root Ganglion Stimulation for Lower Extremity Neuropathic Pain Syndromes: An Evidence-Based Literature Review (Advances in Therapy, 2022) ↩︎
90. De Andres et al, Intrathecal Drug Delivery: Advances and Applications in the Management of Chronic Pain Patient (Frontiers in Pain Research, 2022) ↩︎
91. Ko et al, Intrathecal baclofen pump implantation for complex regional pain syndrome (Anesthesia and Pain Medicine, 2018) ↩︎
92. Seo et al, Implantable Intrathecal Drug Delivery Pump in Complex Regional Pain Syndrome Patient −A case report− (Korean Journal of Pain, 2009) ↩︎
93. Herring et al, Long-term Outcomes Using Intrathecal Drug Delivery Systems in Complex Regional Pain Syndrome (Pain Medicine, 2019) ↩︎
94. Hagedorn, Atallah, Intrathecal management of complex regional pain syndrome: A case report and literature (Scandinavian Journal of Pain, 2017) ↩︎
95. Graak et al, Evaluation of the efficacy of pulsed electromagnetic field in the management of patients with diabetic polyneuropathy (International Journal of Diabetes in Developing Countries, 2009) ↩︎
96. Tassone et al, Assessing the Effects of Pulsed Electromagnetic Therapy on Painful Diabetic Distal Symmetric Peripheral Neuropathy: A Double-Blind Randomized Controlled Trial (SageJournals, 2023) ↩︎
97. Battecha, Efficacy of pulsed electromagnetic field on pain and nerve conduction velocity in patients with diabetic neuropathy (Bulletin of Faculty of Physical Therapy, 2017) ↩︎
98. Beck-Broichsitter et al, Does Pulsed Magnetic Field Therapy Influence Nerve Regeneration in the Median Nerve Model of the Rat? (BioMed Research International, 2014) ↩︎
99. Flatscher et al, Pulsed Electromagnetic Fields (PEMF)—Physiological Response and Its Potential in Trauma Treatment (International Journal of Molecular Sciences, 2023) ↩︎
100. Markovic et al, Effects of pulsed electromagnetic field therapy on outcomes associated with osteoarthritis (Central European Journal of Medicine, 2022) ↩︎
101. Hu et al, Promising application of Pulsed Electromagnetic Fields (PEMFs) in musculoskeletal disorders (Biomedicine & Pharmacotherapy, 2020) ↩︎
102. Attal et al, Repetitive transcranial magnetic stimulation for neuropathic pain: a randomized multicentre sham-controlled trial (Brain, 2021) ↩︎
103. Yang, Chang, Effect of Repetitive Transcranial Magnetic Stimulation on Pain Management: A Systematic Narrative Review (Frontiers in Neurology, 2020) ↩︎
104. Yang et al, Non-invasive Brain Stimulation for Central Neuropathic Pain (Frontiers in Molecular Neuroscience, 2022) ↩︎
105. Missimer, How to Map Your Own Nervous Sytem: The Polyvagal Theory (Movement Paradigm, 2020) ↩︎
106. Porges, The vagal paradox: A polyvagal solution (Comprehensive Psychoneuroendocrinology, 2023) ↩︎
107. Goebel et al, The Valencia consensus-based adaptation of the IASP complex regional pain syndrome diagnostic criteria (Pain, 2021) ↩︎
108. Coderre, Bennett, A Hypothesis for the Cause of Complex Regional Pain Syndrome – Type I (Reflex Sympathetic Dystrophy): Pain Due to Deep-Tissue Microvascular Pathology (Pain Med, 2010) ↩︎
109. Collard, Gelman, Pathophysiology, Clinical Manifestations, and Prevention of Ischemia-Reperfusion Injury (Anesthesiology, 2001) ↩︎
110. Pizzino et al, Oxidative Stress: Harms and Benefits for Human Health (Oxidative Medicine and Cellular Longevity, 2017) ↩︎
111. Coderre, Bennett, A Hypothesis for the Cause of Complex Regional Pain Syndrome – Type I (Reflex Sympathetic Dystrophy): Pain Due to Deep-Tissue Microvascular Pathology (Pain Medicine, 2010) ↩︎
112. Bean et al, Extent of recovery in the first 12 months of complex regional pain syndrome type-1: A prospective study (European Journal of Pain, 2015) ↩︎
113.  Sakakibara, Yamada, Vibration syndrome and autonomic nervous system (Central European Journal of Public Health, 1995) ↩︎
114. Musa, Qurie, Raynaud Disease (StatPearls, 2023) ↩︎
115. Temprano, A Review of Raynaud’s Disease (Missouri Medicine, 2016) ↩︎
116. Harden et al, Validation of proposed diagnostic criteria (the “Budapest Criteria”) for Complex Regional Pain Syndrome (Pain, 2010) ↩︎
117. Schlereth et al, Hyperhidrosis—Causes and Treatment of Enhanced Sweating (Deutsches Arzteblatt International, 2009) ↩︎
118. Russo et al, A new hypothesis for the pathophysiology of complex regional pain syndrome (Medical Hypotheses, 2019) ↩︎
119. Kortekaas et al, Pathophysiological Mechanisms Involved in Vasomotor Disturbances in Complex Regional Pain Syndrome and Implications for Therapy: A Review (Pain Practice, 2016) ↩︎
120. Dayan et al, Exaggerated vasoconstriction in complex regional pain syndrome-1 is associated with impaired resistance artery endothelial function and local vascular reflexes (Journal of Rheumatology, 2008) ↩︎
121. Coderre, Bennett, A Hypothesis for the Cause of Complex Regional Pain Syndrome – Type I (Reflex Sympathetic Dystrophy): Pain Due to Deep-Tissue Microvascular Pathology (Pain Medicine, 2010) ↩︎
122. Coderre, Bennett, A Hypothesis for the Cause of Complex Regional Pain Syndrome – Type I (Reflex Sympathetic Dystrophy): Pain Due to Deep-Tissue Microvascular Pathology (Pain Medicine, 2010) ↩︎
123. Taylor et al, Complex Regional Pain Syndrome: A Comprehensive Review (Pain and Therapy, 2021) ↩︎
124. Ackerman, Zhang, Efficacy of stellate ganglion blockade for the management of type 1 complex regional pain syndrome (Southern Medical Journal, 2006) ↩︎
125. Xu et al, Prediction of the Efficacy of Lumbar Sympathetic Block in Patients with Lower Extremity Complex Regional Pain Syndrome Type 1 Based on the Sympathetic Skin Response (Pain and Therapy, 2023) ↩︎
126. van Eijs et al, Predictors of Pain Relieving Response to Sympathetic Blockade in Complex Regional Pain Syndrome Type 1 (Anesthesiology, 2012) ↩︎
127. Cheng et al, Outcomes of Sympathetic Blocks in the Management of Complex Regional Pain Syndrome: A Retrospective Cohort Study (Pain Medicine, 2019) ↩︎
128. Xu et al, Prediction of the Efficacy of Lumbar Sympathetic Block in Patients with Lower Extremity Complex Regional Pain Syndrome Type 1 Based on the Sympathetic Skin Response (Pain and Therapy, 2023) ↩︎
129. Rho et al, Complex Regional Pain Syndrome (Concise Review for Clinicians, 2002) ↩︎
130. Harden et al, Validation of proposed diagnostic criteria (the “Budapest Criteria”) for Complex Regional Pain Syndrome (Pain, 2010) ↩︎
131. Hooshmand, Phillips, Various Complications of Complex Regional Pain Syndrome (Neurological Associates Pain Management) ↩︎
132. Edinger, Schwartzman, Gardner-Diamond syndrome associated with complex regional pain syndrome (Journal of Dermatological Case Reports, 2013) ↩︎
133. Hooshmand, Phillips, Various Complications of Complex Regional Pain Syndrome (Neurological Associates Pain Management) ↩︎
134. van der Laan et al, Severe complications of reflex sympathetic dystrophy: Infection, ulcers, chronic edema, dystonia, and myoclonus (Physical Medicine and Rehabilitation, 1998) ↩︎
135. Limacher-Riebold, Why comfort zone and stretching zone can be (almost) one (Ute’s Academy, 2021) ↩︎
136. Gad et al, Jojoba Oil: An Updated Comprehensive Review on Chemistry, Pharmaceutical Uses, and Toxicity (Polymers, 2021) ↩︎
137. Stone, Medilan: a hypoallergenic lanolin for emollient therapy (British Journal of Nursing, 2013) ↩︎
138. Burr, Emollients for managing dry skin conditions (Professional Nurse, 1999) ↩︎
139. Dyble, Ashton, Use of emollients in the treatment of dry skin conditions (British Journal of Community Nursing, 2011) ↩︎
140. Carrer et al, Lanolin-Based Synthetic Membranes as Percutaneous Absorption Models for Transdermal Drug Delivery (Pharmaceutics, 2018) ↩︎
141. Torres et al, How to Promote Skin Repair? In-Depth Look at Pharmaceutical and Cosmetic Strategies (Pharmaceuticals, 2023) ↩︎
142. Mathieson et al, Content and sentiment analysis of gabapentinoid-related tweets: An infodemiology study (Drug and Alcohol Review, 2022) ↩︎
143. Salimzade et al, Comparative effects of chronic administrations of gabapentin, pregabalin and baclofen on rat memory using object recognition test (Research in Pharmaceutical Sciences, 2017) ↩︎
144. Castillo et al, Severity of Topiramate-Related Working Memory Impairment is Modulated by Plasma Concentration and Working Memory Capacity (Journal of Clinical Pharmacology, 2020) ↩︎
145. Egel et al, Isolated Cataplexy in the Differential Diagnosis of Drop Attacks: A Case of Successful Clinical Diagnosis and Treatment (Case Reports in Neurological Medicine, 2012) ↩︎
146. Reynolds, Roy, Isolated Cataplexy and REM Sleep Behavior Disorder After Pontine Stroke (Journal of Clinical Sleep Medicine, 2011) ↩︎
147. Wang et al, The Orexin/Receptor System: Molecular Mechanism and Therapeutic Potential for Neurological Diseases (Frontiers in Molecular Neuroscience, 2018) ↩︎
148. Dauvilliers et al, Cataplexy—clinical aspects, pathophysiology and management strategy (US Department of Veterans Affairs, 2014) ↩︎
149. Schwartzman, Complex Regional Pain Syndrome: Systemic Complications (Practical Pain Management, 2014) ↩︎
150. Coderre, Bennett, A Hypothesis for the Cause of Complex Regional Pain Syndrome – Type I (Reflex Sympathetic Dystrophy): Pain Due to Deep-Tissue Microvascular Pathology (Pain Medicine, 2015) ↩︎
151. Varenna, Crotti, Targeting the bone in the treatment of complex regional pain syndrome: In depth – The truth? (Journal of Orthopaedics Trauma Surgery and Related Research, 2018) ↩︎
152. Okumo et al, Senso-Immunologic Prospects for Complex Regional Pain Syndrome Treatment (Frontiers in Immunology, 2022) ↩︎
153. Tetsuya et al, Bone atrophy in complex regional pain syndrome patients measured by microdensitometry (Canadian Journal of Anaesthesia, 1998) ↩︎
154. Kollman et al, The role of the bone in complex regional pain syndrome 1—A systematic review (European Journal of Pain, 2023) ↩︎
155. Mussawy et al, Evaluation of bone microstructure in CRPS-affected upper limbs by HR-pQCT (Clinical Cases in Mineral and Bone Metabolism, 2017) ↩︎
156. Varenna, Crotti, Targeting the bone in the treatment of complex regional pain syndrome: In depth – The truth? (Journal of Orthopaedics Trauma Surgery and Related Research, 2018) ↩︎
157. Kozin et al, The reflex sympathetic dystrophy syndrome II. Roentgenographic and scintigraphic evidence of bilaterality and of periarticular accentuation (American Journal of Medicine, 1976) ↩︎
158. Tetef, Connecting Ehler’s-Danlos Syndrome and Complex Regional Pain Syndrome (Practical Pain Management, 2023) ↩︎
159. Stoler, Oaklander, Patients with Ehlers Danlos syndrome and CRPS: A possible association? (Pain, 2006) ↩︎
160. Cheon et al, Diagnostic Performance of Three-Phase Bone Scintigraphy and Digital Infrared Thermography Imaging for Chronic Post-Traumatic Complex Regional Pain Syndrome (Diagnostics, 2021) ↩︎
161. Okumo et al, Senso-Immunologic Prospects for Complex Regional Pain Syndrome Treatment (Frontiers in Immunology, 2022) ↩︎
162. Rasmussen et al, Atypical Chest Pain: Evidence of Intercostobrachial Nerve Sensitization in Complex Regional Pain Syndrome (Pain Physician, 2009) ↩︎
163. Schwartzman, Complex Regional Pain Syndrome: Systemic Complications (Practical Pain Management, 2013) ↩︎
164. Irwin, Schwartzman, Complex regional pain syndrome with associated chest wall dystonia: a case report (Journal of Brachial Plexus and Peripheral Nerve Injury, 2011) ↩︎
165. Terkelsen et al, Heart Rate Variability in Complex Regional Pain Syndrome during Rest and Mental and Orthostatic Stress (Pain Medicine, 2012) ↩︎
166. Bartur et al, Heart Rate Autonomic Regulation System at Rest and During Paced Breathing among Patients with CRPS as Compared to Age-Matched Healthy Controls (Pain Medicine, 2014) ↩︎
167. Smith et al, Syncope in Complex Regional Pain Syndrome (Clinical Cardiology, 2011) ↩︎
168. Schwartzman, Complex Regional Pain Syndrome: Systemic Complications (Practical Pain Management, 2013) ↩︎
169. Magnus et al, From a Symptom-Based to a Mechanism-Based Pharmacotherapeutic Treatment in Complex Regional Pain Syndrome (Drugs, 2022) ↩︎
170. Coderre, Bennett, A Hypothesis for the Cause of Complex Regional Pain Syndrome – Type I (Reflex Sympathetic Dystrophy): Pain Due to Deep-Tissue Microvascular Pathology (Pain Medicine, 2010) ↩︎
171. Hooshmand, Phillips, Various Complications of Complex Regional Pain Syndrome (Neurological Associates Pain Management) ↩︎
172. Desai et al, PAIN-INDUCED HYPERTENSION CAUSING POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (Critical Care Medicine, 2016) ↩︎
173. Groenweg et al, Regulation of peripheral blood flow in Complex Regional Pain Syndrome: clinical implication for symptomatic relief and pain management (BMC Musculoskeletal Disorders, 2009) ↩︎
174. Palma, Kaufmann, Treatment of orthostatic and postprandial hypotension (UpToDate, 2023) ↩︎
175. Porges, Polyvagal Theory: A Science of Safety (Frontiers Integrative Neuroscience, 2022) ↩︎
176. Pinna, Edwards, A Systematic Review of Associations Between Interoception, Vagal Tone, and Emotional Regulation: Potential Applications for Mental Health, Wellbeing, Psychological Flexibility, and Chronic Conditions (Frontiers in Psychology, 2020) ↩︎
177. Larkin et al, Cardiac Vagal Tone and Stress (Neuroscience, 2021) ↩︎
178. Zhang et al, Exercise for Neuropathic Pain: A Systematic Review and Expert Consensus (Frontiers in Medicine, 2021) ↩︎
179. Leitzelar, Koltyn, Exercise and Neuropathic Pain: A General Overview of Preclinical and Clinical Research (Sports Medicine Open, 2021) ↩︎
180. Cooper et al, Emerging Relationships between Exercise, Sensory Nerves, and Neuropathic Pain (Frontiers in Neuroscience, 2016) ↩︎
181. Sleijser-Koehorst et al, The effects of aerobic exercise on neuroimmune responses in animals with traumatic peripheral nerve injury: a systematic review with meta-analyses (Journal of Neuroinflammation, 2023) ↩︎
182. Kluding et al, Safety of Aerobic Exercise in People With Diabetic Peripheral Neuropathy: Single-Group Clinical Trial (Physical Therapy, 2015) ↩︎
183. Naimat-Ullah et al, The Effect of Aerobic Exercises on Pain in Patients with Diabetic Peripheral Neuropathy (Pakistan Journal of Medical & Health Sciences, 2022) ↩︎
184. Hooshmand, Phillips, Various Complications of Complex Regional Pain Syndrome (Neurological Associates Pain Management) ↩︎
185. Schwartzman, Complex Regional Pain Syndrome: Systemic Complications (Practical Pain Management, 2013) ↩︎
186. Duan et al, Regulation of the Autonomic Nervous System on Intestine (Frontiers in Physiology, 2021) ↩︎
187. Schaper et al, Regional Sympathetic Blockade Attenuates Activation of Intestinal Macrophages and Reduces Gut Barrier Failure (Critical Care Medicine, 2013) ↩︎
188. Browning, Travagli, Central Nervous System Control of Gastrointestinal Motility and Secretion and Modulation of Gastrointestinal Functions (Comprehensive Physiology, 2014) ↩︎
189. Dhana et al, MIND diet, common brain pathologies, and cognition in community-dwelling older adults (Journal of Alzheimer’s Disease, 2021) ↩︎
190. Morris et al, MIND Diet Associated with Reduced Incidence of Alzheimer’s Disease (Alzheimers Dementia, 2015) ↩︎
191. Bodke, Jogdand, Role of Probiotics in Human Health (Cureus, 2022) ↩︎
192. Nagpal et al, Probiotics, their health benefits and applications for developing healthier foods: a review (Microbiology Letters, 2012) ↩︎
193. Das et al, Current status of probiotic and related health benefits (Applied Food Research, 2022) ↩︎
194. Wang et al, Abdominal massage: A review of clinical and experimental studies from 1990 to 2021 (Complementary Therapies in Medicine, 2022) ↩︎
195. Gu et al, Analysis of the efficacy of abdominal massage on functional constipation: A meta-analysis (Heliyon, 2023) ↩︎
196. Lamas et al, Effects of abdominal massage in management of constipation—A randomized controlled trial (International Journal of Nursing Studies, 2009) ↩︎
197. Turan, Atabek Aşt, The Effect of Abdominal Massage on Constipation and Quality of Life (Gastroenterology Nursing, 2016) ↩︎
198. Hu et al, Effects of Manual Therapy on Bowel Function of Patients with Spinal Cord Injury (Journal of Physical Therapy Science, 2013) ↩︎
199. Huang et al, Abdominal massage alleviates functional diarrhea in immature rats via modulation of intestinal microbiota and tight junction protein (Frontiers in Pediatrics, 2022) ↩︎
200. Ashok, Gluten, Inflammation, and Neurodegeneration (American Journal of Lifestyle Medicine, 2022) ↩︎
201. Rizwan et al, Dietary wheat gluten induces astro- and microgliosis in the hypothalamus of male mice (Journal of Neuroendocrinology, 2023) ↩︎
202. Janicki, Chronic Pelvic Pain as a Form of Complex Regional Pain Syndrome (Clinical Obstetrics and Gynecology, 2003) ↩︎
203. Micheal, Hunter, Chronic Pelvic Pain as a Form of Complex Regional Pain Syndrome (Practical Pain Management, 2019) ↩︎
204. Schattschneider et al, Endothelial dysfunction in cold type complex regional pain syndrome (Neurology, 2006) ↩︎
205. Duman et al, Assessment of endothelial function in complex regional pain syndrome type I (Rheumatology International, 2008) ↩︎
206. Ostergaard et al, Capillary dysfunction and impaired tissue oxygenation in complex regional pain syndrome: A hypothesis (Pain, 2014) ↩︎
207. van den Berg et al, Complex regional pain syndrome type 1 may be associated with menstrual cycle disorders: A case–control study (Complementary Therapies in Medicine, 2009) ↩︎
208. Trikha et al, Complex regional pain syndrome and pregnancy (Journal of Obstetric Anaesthesia and Critical Care, 2013) ↩︎
209. Campanharo et al, Complex regional pain syndrome and pregnancy (Open Access Texts, 2021) ↩︎
210. Yoo et al, Pregnancy in Woman with Spinal Cord Stimulator for Complex Regional Pain Syndrome: A Case Report and Review of the Literature (Korean Journal of Pain, 2010) ↩︎
211. Jozwiak, Hong, Complex Regional Pain Syndrome Management: An Evaluation of the Risks and Benefits of Spinal Cord Stimulator Use in Pregnancy (Pain Practice, 2020) ↩︎
212. Turner-Stokes, Reflex sympathetic dystrophy–a complex regional pain syndrome (Disability and Rehabilitation, 2002) ↩︎
213. Schulten et al, Chronic pain syndrome of the penis following cerebrovascular insult (Anasthesiol Intensivmed Notfallmed Schmerzther, 2001) ↩︎
214. Kim et al, A Case of Complex Regional Pain Syndrome Type I after Urethroplasty Treated by Ganglion Impar Block: A case report (Journal or Korean Pain Society, 2004) ↩︎
215. Chancellor et al, Urological Symptomatology in Patients with Reflex Sympathetic Dystrophy (Journal of Urology, 1996) ↩︎
216. Schwartzman, Complex Regional Pain Syndrome: Systemic Complications (Practical Pain Management, 2013) ↩︎
217. Wang, Lefevre, Management of Urinary and Fecal Incontinence in Patients With Complex Regional Pain Syndrome (Female Pelvic Medicine & Reconstructive Surgery, 2016) ↩︎
218. Charrua et al, Sympathetic nervous system and chronic bladder pain: a new tune for an old song (Translational Andrology and Urology, 2015) ↩︎
219. Coderre, Bennett, A Hypothesis for the Cause of Complex Regional Pain Syndrome – Type I (Reflex Sympathetic Dystrophy): Pain Due to Deep-Tissue Microvascular Pathology (Pain Medicine, 2010) ↩︎
220. Tan et al, Impaired Oxygen Utilization in Skeletal Muscle of CRPS I Patients (Journal of Surgical Research, 2012) ↩︎
221. Birklein et al, Increased skin lactate in complex regional pain syndrome: Evidence for tissue hypoxia? (Neurology, 2000) ↩︎
222. Heerschap et al, Metabolic changes in reflex sympathetic dystrophy: A 31P NMR spectroscopy study (Muscle & Nerve, 1993) ↩︎
223. Tan et al, Mitochondrial dysfunction in muscle tissue of complex regional pain syndrome type I patients (European Journal of Pain, 2012) ↩︎
224. Chagn et al, Comparison of the effects between lasers applied to myofascial trigger points and to classical acupoints for patients with cervical myofascial pain syndrome (Biomedical Journal, 2020) ↩︎
225. Shahimoridi et al, The Effectiveness of the Polarized Low-Level Laser in the Treatment of Patients With Myofascial Trigger Points in the Trapezius Muscles (Journal of Lasers in Medical Sciences, 2020) ↩︎
226. Oliveira et al, Clinical effectiveness evaluation of laser therapy and dry needling
     in treatment of patients with myofascial pain in masseter muscle (International Journal of Orofacial Myology and Myofunctional Therapy, 2018) ↩︎
227. Agung et al, Low-level laser therapy and dry needling for myofascial pain syndrome of the upper trapezius muscle: An interventional study (Journal of Physics: Conference Series, 2018) ↩︎
228. Hooshmand, Physical Therapy Part I (Neurological Associate Pain Management) ↩︎
229. Hooshmand, Physical Therapy Part II (Neurological Associate Pain Management) ↩︎
230. Taylor et al, Complex Regional Pain Syndrome: A Comprehensive Review (Pain and Therapy, 2021) ↩︎
231. Misidou, Papagoras, Complex Regional Pain Syndrome: An update (Mediterranean Journal of Rheumatology, 2019) ↩︎
232. Dirckx et al, Inflammation in cold complex regional pain syndrome (Anaesthesiologica Scandinavica, 2015) ↩︎
233. Clark et al, Autoinflammatory and autoimmune contributions to complex regional pain syndrome (Molecular Pain, 2018) ↩︎
234. Russo et al, A new hypothesis for the pathophysiology of complex regional pain syndrome (Medical Hypotheses, 2018) ↩︎
235. Huygen et al, Evidence for local inflammation in complex regional pain syndrome type 1 (Mediators of Inflammation, 2002) ↩︎
236. Birklein et al, Activation of cutaneous immune responses in complex regional pain syndrome (Journal of Pain, 2015) ↩︎
237. Groeneweg et al, Increased endothelin-1 and diminished nitric oxide levels in blister fluids of patients with intermediate cold type complex regional pain syndrome type 1 (BMC Musculoskeletal Disorders, 2006) ↩︎
238. Wei et al, Pentoxifylline attenuates nociceptive sensitization and cytokine expression in a tibia fracture rat model of complex regional pain syndrome (European Journal of Pain, 2009) ↩︎
239. Sabsovich et al, TNF signaling contributes to the development of nociceptive sensitization in a tibia fracture model of complex regional pain syndrome type I (Pain, 2008) ↩︎
240. Li et al, The NALP1 inflammasome controls cytokine production and nociception in a rat fracture model of complex regional pain syndrome (Pain, 2009) ↩︎
241. Li et al, Fracture induces keratinocyte activation, proliferation, and expression of pronociceptive inflammatory mediators (Pain, 2010) ↩︎
242. Guo et al, Oxidative stress contributes to fracture/cast-induced inflammation and pain in a rat model of complex regional pain syndrome (Journal of Pain, 2018) ↩︎
243. Schlereth et al, Inflammation in CRPS: role of the sympathetic supply (Autonomic Neuroscience, 2014) ↩︎
244. Calder et al, Evidence for immune system involvement in reflex sympathetic dystrophy (The Journal of Hand Surgery: British & European Volume, 1998) ↩︎
245. Li et al, Neuropeptide regulation of adaptive immunity in the tibia fracture model of complex regional pain syndrome (Journal of Neuroinflammation, 2018) ↩︎
246. Osborne et al, Cutaneous immunopathology of long-standing complex regional pain syndrome (European Journal of Pain, 2015) ↩︎
247. Dubuis et al, Longstanding complex regional pain syndrome is associated with activating autoantibodies against alpha-1a adrenoceptors (Pain, 2014) ↩︎
248. Kohr et al, Autoimmunity against the β2 adrenergic receptor and muscarinic-2 receptor in complex regional pain syndrome (Pain, 2011) ↩︎
249. Dharmalingam et al, Autoantibodies from patients with complex regional pain syndrome induce pro-inflammatory effects and functional disturbances on endothelial cells in vitro (Pain, 2022) ↩︎
250. Kohr et al, Autoimmunity against the β2 adrenergic receptor and muscarinic-2 receptor in complex regional pain syndrome (Pain, 2011) ↩︎
251. Kudlak, Tadi, Physiology, Muscarinic Receptor (StatPearls, 2023) ↩︎
252. Cuhadar et al, Autoantibodies produce pain in complex regional pain syndrome by sensitizing nociceptors (Pain, 2019) ↩︎
253. Baerlecken et al, Autoantibodies against P29ING4 are associated with complex regional pain syndrome (Immunologic Research, 2020) ↩︎
254. Blaes et al, Autoimmune etiology of complex regional pain syndrome (Neurology, 2004) ↩︎
255. Wen-Wu et al, Neuropeptide regulation of adaptive immunity in the tibia fracture model of complex regional pain syndrome (Journal of Neuroinflammation, 2018) ↩︎
256. Dirckx et al, The Prevalence of Autoantibodies in Complex Regional Pain Syndrome Type I (Mediators of Inflammation, 2015) ↩︎
257. Helyes et al, Transfer of complex regional pain syndrome to mice via human autoantibodies is mediated by interleukin-1–induced mechanisms (Biological Sciences, 2019) ↩︎
258. Sahbaie et al, Autonomic Regulation of Nociceptive and Immunologic Changes in a Mouse Model of Complex Regional Pain Syndrome (Journal of Pain, 2022) ↩︎
259. Okumo et al, Senso-Immunologic Prospects for Complex Regional Pain Syndrome Treatment (Frontiers in Immunology, 2022) ↩︎
260. Goebels, Blaes, Complex regional pain syndrome, prototype of a novel kind of autoimmune disease (Autoimmunity Reviews, 2013) ↩︎
261. Mahroum, Shoenfeld, Autoimmune Autonomic Dysfunction Syndromes: Potential Involvement and Pathophysiology Related to Complex Regional Pain Syndrome, Fibromyalgia, Chronic Fatigue Syndrome, Silicone Breast Implant–Related Symptoms and Post-COVID Syndrome (Pathophysiology, 2022) ↩︎
262. Colonna, Butovsky, Microglia Function in the Central Nervous System During Health and Neurodegeneration (Annual Review of Immunology, 2017) ↩︎
263. Prasad, Chakravarthy, Review of complex regional pain syndrome and the role of the neuroimmune axis (Molecular Pain, 2021) ↩︎
264. Haight et al, Of mice, microglia, and (wo)men: a case series and mechanistic investigation of hydroxychloroquine for complex regional pain syndrome (Pain Reports, 2020) ↩︎
265. Cooper, Clark, Neuroinflammation, Neuroautoimmunity, and the Co-Morbidities of Complex Regional Pain Syndrome (Journal of Neuroimmune Pharmacology, 2012) ↩︎
266. Linnman et al, Inflaming the Brain: CRPS a model disease to understand Neuroimmune interactions in Chronic Pain (Journal of Neuroimmune Pharmacology, 2012) ↩︎
267. Dirckx et al, Effect of Immunomodulating Medications in Complex Regional Pain Syndrome
     A Systematic Review (Clinical Journal of Pain, 2012) ↩︎
268. Linnman et al, Inflaming the Brain: CRPS a model disease to understand Neuroimmune interactions in Chronic Pain (Journal of Neuroimmune Pharmacology, 2012) ↩︎
269. McKenzie-Brown et al, Low-Dose Naltrexone (LDN) for Chronic Pain at a Single Institution: A Case Series (Journal of Pain Research, 2023) ↩︎
270. Chopra, Cooper, Treatment of Complex Regional Pain Syndrome (CRPS) Using Low Dose Naltrexone (LDN) (Journal of Neuroimmune Pharmacology, 2013) ↩︎
271. Rupp et al, Low-dose naltrexone’s utility for non-cancer centralized pain conditions: a scoping review (Pain Medicine, 2023) ↩︎
272. Giorgi et al, Cannabis and Autoimmunity: Possible Mechanisms of Action (Immunotargets Therapy, 2021) ↩︎
273. Petzke et al, Cannabis-Based Medicines and Medical Cannabis for Chronic Neuropathic Pain (CNS Drugs, 2021) ↩︎
274. Lowe et al, Cannabis for peripheral neuropathy: The good, the bad, and the unknown (Cleveland Clinic Journal of Medicine, 2018) ↩︎
275. Wilsey et al, Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain (Journal of Pain, 2012) ↩︎
276. Chang et al, Medical Cannabis for Chronic Noncancer Pain: A Systematic Review of Health Care Recommendations (Pain Research and Management, 2020) ↩︎
277. Almog et al, The pharmacokinetics, efficacy, and safety of a novel selective-dose cannabis inhaler in patients with chronic pain: A randomized, double-blinded, placebo-controlled trial (European Journal of Pain, 2020) ↩︎
278. Barbalinardo et al, The Treatment of Longstanding Complex Regional Pain Syndrome with Oral Steroids (Pain Medicine, 2016) ↩︎
279. Jamroz et al, Prednisone for Acute Complex Regional Pain Syndrome: A Retrospective Cohort Study (Pain Research and Management, 2020) ↩︎
280. Samantha-Su et al, Complex Regional Pain Syndrome: A Comprehensive Review (Pain and Therapy, 2021) ↩︎
281. Tetef, Complex Regional Pain Syndrome-Induced Hyperparathyroidism: A Case Study (Practical Pain Management, 2022) ↩︎
282. Grijalva et al, Fludrocortisone Is Associated With a Higher Risk of All‐Cause Hospitalizations Compared With Midodrine in Patients With Orthostatic Hypotension (Journal of American Heart Association, 2017) ↩︎
283. Rowe et al, Fludrocortisone Acetate to Treat Neurally Mediated Hypotension in Chronic Fatigue Syndrome: A Randomized Controlled Trial (JAMA, 2001) ↩︎
284. Veazie et al, Fludrocortisone for orthostatic hypotension (Cochrane Database of Systematic Reviews, 2021) ↩︎
285. Esposito et al, Primary Adrenal Insufficiency: Managing Mineralocorticoid Replacement Therapy (Journal of Clinical Endocrinology and Metabolism, 2017) ↩︎
286. Hooshmand, Phillips, Various Complications of Complex Regional Pain Syndrome (CRPS) (Neurological Associates Pain Management Center) ↩︎
287. Drummond, Finch, Photophobia in complex regional pain syndrome: visual discomfort is greater on the affected than unaffected side (Pain, 2021) ↩︎
288. Ten Brink, Bultitude, Visual Sensitivity in Complex Regional Pain Syndrome and Fibromyalgia: An Online Study (Perception, 2022) ↩︎
289. Ebrahiminadib et al, Ocular Neuropathic Pain: An Overview Focusing on Ocular Surface Pains (Clinical Ophthalmology, 2020) ↩︎
290. Galor et al, Neuropathic ocular pain: an important yet underevaluated feature of dry eye (Eye, 2015) ↩︎
291. Williamson et al, Increased Risk of Ophthalmic Disease in Patients with Complex Regional Pain Syndrome (Investigative Ophthalmology & Visual Science, 2014) ↩︎
292. Wood, Shedding new light on visual snow syndrome (Nature Reviews Neurology, 2020) ↩︎
293. Klein, Schankin, Visual Snow Syndrome as a Network Disorder: A Systematic Review (Frontiers in Neurology, 2021) ↩︎
294. Silva, Puledda, Visual snow syndrome and migraine: a review (Eye, 2023) ↩︎
295. Hooshmand, Phillips, Various Complications of Complex Regional Pain Syndrome (CRPS) (Neurological Associates Pain Management Center) ↩︎
296. Drummond, Finch, Auditory disturbances in patients with complex regional pain syndrome (Pain, 2023) ↩︎
297. Drummond et al, The Specificity and Mechanisms of Hemilateral Sensory Disturbances in Complex Regional Pain Syndrome (Journal of Pain, 2011) ↩︎
298. de Klaver et al, Hyperacusis in patients with complex regional pain syndrome related dystonia (Journal of Neurology, Neurosurgery, & Psychiatry, 2007) ↩︎
299. Drummond, A possible role of the locus coeruleus in complex regional pain syndrome (Frontiers in Integrative Neuroscience, 2012) ↩︎
300. Noseda et al, Migraine photophobia originating in cone-driven retinal pathways (BRAIN, 2016) ↩︎
301. Blackburn et al, FL-41 Tint Improves Blink Frequency, Light Sensitivity, and Functional Limitations in Patients with Benign Essential Blepharospasm (Ophthalmology, 2010) ↩︎
302. Pacheco, Singh, Can Pink Noise Help You Sleep? (Sleep Foundation, 2023) ↩︎
303. Sarow, White, Brown, Pink and Green Noise: Benefits of Each (Soundly, 2023) ↩︎
304. Peterlin et al, Migraine may be a risk factor for the development of complex regional pain syndrome (Cephalalgia, 2010) ↩︎
305. Stanford Comparative Pain Scale ↩︎
306. Fusayasu et al, Increased plasma substance P and CGRP levels, and high ACE activity in migraineurs during headache-free periods (Pain, 2007) ↩︎
307. Starr et al, A reactive oxygen species-mediated component in neurogenic vasodilatation (Cardiovascular Research, 2008) ↩︎
308. Birklein et al, The important role of neuropeptides in complex regional pain syndrome (Neurology, 2001) ↩︎
309. Fusco et al, Neurogenic inflammation in primary headaches (Neurological Sciences, 2003) ↩︎
310. Theoharides et al, The role of mast cells in migraine pathophysiology (Brain Research, 2005) ↩︎
311. de Mos et al, Medical history and the onset of complex regional pain syndrome (CRPS) (Pain, 2008) ↩︎
312. Visser et al, Is migraine a complex regional pain syndrome of the brain? Migraine prophylaxis with vitamin C? (Pain Practice, 2011) ↩︎
313. Ray, Singhi, Complex regional pain syndrome type 1 in a child with migraine (Journal of Child Neurology, 2011) ↩︎
314. Cuadrado et al, Migrainous corpalgia: body pain and allodynia associated with migraine attacks (Cephalalgia, 2008) ↩︎
315. Burstein et al, An association between migraine and cutaneous allodynia (Annals of Neurology, 2000) ↩︎
316. Thoma et al, Impaired Pain Processing at a Brainstem Level Is Involved in Maladaptive Neuroplasticity in Patients with Chronic Complex Regional Pain Syndrome (International Journal of Molecular Sciences, 2022) ↩︎
317. Olesen et al, Origin of pain in migraine: evidence for peripheral sensitisation (Lancet Neurology, 2009) ↩︎
318. Sacco et al, Peripheral vascular dysfunction in migraine: a review (Journal of Headache and Pain, 2013) ↩︎
319. Jacobs, Dussor, Neurovascular contributions to migraine: moving beyond vasodilation (Neuroscience, 2016) ↩︎
320. Mason, Russo, Vascular Contributions to Migraine: Time to Revisit? (Frontiers in Cellular Neuroscience, 2018) ↩︎
321. Zakrzewska, Linskey, Trigeminal Neuralgia (American Family Physician, 2016) ↩︎
322. Safitri, Trigeminal Neuralgia: A Brief Review (European Journal of Medical & Health Services, 2023) ↩︎
323. De Toledo et al, Prevalence of trigeminal neuralgia: A systematic review (The Journal of the American Dental Association, 2016) ↩︎
324. Wettervik et al, Incidence of trigeminal neuralgia: A population-based study in Central Sweden (European Journal of Pain, 2023) ↩︎
325. de Mos et al, The incidence of complex regional pain syndrome: a population-based study (Pain, 2007) ↩︎
326. Lee et al, A Korean nationwide investigation of the national trend of complex regional pain syndrome (Korean Journal of Pain, 2021) ↩︎
327. Sandroni et al, Complex regional pain syndrome type I: incidence and prevalence in Olmsted county, a population-based study (Pain, 2003) ↩︎
328. Kim et al, Epidemiology of complex regional pain syndrome in Korea: An electronic population health data study (Plos One, 2018) ↩︎
329. Szok et al, Chronic Migraine as a Primary Chronic Pain Syndrome and Recommended Prophylactic Therapeutic Options: A Literature Review (life, 2023) ↩︎
330. Mungoven et al, Chronic Migraine Pathophysiology and Treatment: A Review of Current Perspectives (Frontiers in Pain Research, 2021) ↩︎
331. Agonstoni et al, Current and emerging evidence-based treatment options in chronic migraine: a narrative review (Journal of Headache and Pain, 2019) ↩︎
332. Noseda et al, Migraine photophobia originating in cone-driven retinal pathways (BRAIN, 2016) ↩︎
333. Khorsha et al, Association of drinking water and migraine headache severity (Journal of Clinical Neuroscience, 2020) ↩︎
334. Arca, Singh, Dehydration and Headache (Current Pain and Headache Reports, 2021) ↩︎
335. Martins, Gouveia, More on Water and Migraine (Sage Journals, 2007) ↩︎
336. Galer et al, Course of Symptoms and Quality of Life Measurement in Complex Regional Pain Syndrome: A Pilot Survey (Journal of Pain and Symptom Management, 2000) ↩︎
337. Jaemoon et al, Multicenter survey of symptoms, work life, economic status, and quality of life of complex regional pain syndrome patients (Korean Journal of Pain, 2021) ↩︎
338. Sharma et al, A web-based cross-sectional epidemiological survey of complex regional pain syndrome (Regional Anesthesia and Pain Medicine, 2009) ↩︎
339. Lee et al, Risk Factors for Suicidal Ideation among Patients with Complex Regional Pain Syndrome (Psychiatry Investigation, 2014) ↩︎
340. Gallicchio, Kalesan, Sleep duration and mortality: a systematic review and meta-analysis (Journal of Sleep Research, 2009) ↩︎
341. Grander et al, Habitual Sleep Duration Associated with Self-Reported and Objectively-Determined Cardiometabolic Risk Factors (Sleep Medicine, 2013) ↩︎
342. Lee et al, Risk Factors for Suicidal Ideation among Patients with Complex Regional Pain Syndrome (Psychiatry Investigation, 2014) ↩︎
343. Chunlong et al, Functional Connectivity Disturbances of the Locus Coeruleus in Chronic Insomnia Disorder (Nature and Science of Sleep, 2022) ↩︎
344. Rolls, The functions of the orbitofrontal cortex (Brain and Cognition, 2004) ↩︎
345. Wallis, Cross-species studies of orbitofrontal cortex and value-based decision-making (Nature Neuroscience, 2012) ↩︎
346. Torregrossa et al, Impulsivity, Compulsivity, and Habit: The Role of Orbitofrontal Cortex Revisited (Biological Psychiatry, 2008) ↩︎
347. Andersen et al, Sleep Disturbance and Pain: A Tale of Two Common Problems (Chest, 2018) ↩︎
348. Harden et al, Complex Regional Pain Syndrome: Practical Diagnostic and Treatment Guidelines, 5th Edition (Pain Medicine, 2022) ↩︎
349. Sindrup, Jensen, Pharmacologic treatment of pain in polyneuropathy (Neurology, 2000) ↩︎
350. McQuay et al, A systematic review of antidepressants in neuropathic pain (Pain, 1996) ↩︎
351. Sindrup et al, The selective serotonin reuptake inhibitor paroxetine is effective in the treatment of diabetic neuropathy symptoms (Pain, 1990) ↩︎
352. Sindrup et al, The selective serotonin reuptake inhibitor citalopram relieves the symptoms of diabetic neuropathy (Clinical Pharmacology and Therapeutics, 1992) ↩︎
353. Benitez et al, Advantages and Disadvantages of Using St. John’s Wort as a Treatment for Depression (Cureus, 2022) ↩︎
354. Apaydin et al, A systematic review of St. John’s wort for major depressive disorder (Systematic Reviews, 2016) ↩︎
355. Forsdike, Pirotta, St John’s wort for depression: scoping review about perceptions and use by general practitioners in clinical practice (Journal of Pharmacy and Pharmacology, 2019) ↩︎
356. Scarff, Managing Psychiatric Symptoms in Patients with Complex Regional Pain Syndrome (Innovations in Clinical Neuroscience, 2022) ↩︎
357. Schmitz, Benzodiazepine use, misuse, and abuse: A review (Mental Health Clinician, 2016) ↩︎
358. Schifano et al, An Insight into Z-Drug Abuse and Dependence: An Examination of Reports to the European Medicines Agency Database of Suspected Adverse Drug Reactions (International Journal of Neuropharmacology, 2019) ↩︎
359. Han et al, Suvorexant, a Novel Dual Orexin Receptor Antagonist, for the Management of Insomnia (Health Psychology Research, 2022) ↩︎
360. Jaing et al, Daridorexant for the treatment of insomnia disorder: A systematic review and meta-analysis of randomized controlled trials (Medicine, 2023) ↩︎
361. Bigalke et al, Orexin, Sleep, Sympathetic Neural Activity, and Cardiovascular Function (Hypertension, 2022) ↩︎
362. Geha et al, The Brain in Chronic CRPS Pain: Abnormal Gray-White Matter Interactions in Emotional and Autonomic Regions (Neuron, 2008) ↩︎
363. Maihofner, DeCol, Decreased perceptual learning ability in complex regional pain syndrome (European Journal of Pain, 2007) ↩︎
364. Apkarian et al, Chronic pain patients are impaired on an emotional decision-making task (Pain, 2004) ↩︎
365. Geha et al, The Brain in Chronic CRPS Pain: Abnormal Gray-White Matter Interactions in Emotional and Autonomic Regions (Neuron, 2008) ↩︎
366. Tajerian, Clark, New Concepts in Complex Regional Pain Syndrome (Hand Clinics, 2016) ↩︎
367. Dilek et al, Anxious personality is a risk factor for developing complex regional pain syndrome type I (Rheumatology International, 2012) ↩︎
368. Bean et al, Relationships between psychological factors, pain, and disability in complex regional pain syndrome and low back pain (Clinical Journal of Pain, 2014) ↩︎
369. Lohnberg, Altmaier, A review of psychosocial factors in complex regional pain syndrome (Journal of Clinical Psychology in Medical Settings, 2013) ↩︎
370. Beerthuizenl et al, The association between psychological factors and the development of complex regional pain syndrome type 1 (CRPS1) — A prospective multicenter study (European Journal of Pain, 2012) ↩︎
371. Wager et al, Psychological distress and stressful life events in pediatric complex regional pain syndrome (Pain Research and Management, 2015) ↩︎
372. Guy-Evans, Amygdala Hijack: How It Works, Signs, & How To Cope (SimplyPsychology, 2023) ↩︎
373. Davies, Flipping your Lid & Widening your Window of Tolerance (VitalityCollective) ↩︎
374. Rosenkranz et al, Chronic stress causes amygdala hyperexcitability in rodents (Biological Psychiatry, 2010) ↩︎
375. Correll et al, Chronic Cold Stress Alters Prefrontal Cortical Modulation of Amygdala Neuronal Activity in Rats (Biological Psychiatry, 2005) ↩︎
376. Zhang et al, Stress-Induced Functional Alterations in Amygdala: Implications for Neuropsychiatric Diseases (Frontiers in Neuroscience, 2018) ↩︎
377. Ressler, Amygdala Activity, Fear, and Anxiety: Modulation by Stress (Biological Psychiatry, 2011) ↩︎
378. Barad et al, Complex Regional Pain Syndrome Is Associated With Structural Abnormalities in Pain-Related Regions of the Human Brain (Journal of Pain, 2014) ↩︎
379. Geha et al, The Brain in Chronic CRPS Pain: Abnormal Gray-White Matter Interactions in Emotional and Autonomic Regions (Neuron, 2008) ↩︎
380. Rinpoche, Understanding the Monkey Mind, Meditation & Monkey Mind, What Meditation Really Is (YouTube, 2021, 2017, 2011) ↩︎
381. Ngô, Review of the effects of mindfulness meditation on mental and physical health and its mechanisms of action (Sante Mentale au Quebec, 2013) ↩︎
382. Rathore et al, Functional Connectivity of Prefrontal Cortex in Various Meditation Techniques – A Mini-Review (International Journal of Yoga, 2022) ↩︎
383. Kozasa et al, Meditation training increases brain efficiency in an attention task (NeuroImage, 2012) ↩︎
384. Tomasino, Fabbro, Increases in the right dorsolateral prefrontal cortex and decreases the rostral prefrontal cortex activation after-8 weeks of focused attention based mindfulness meditation (Brain and Cognition, 2016) ↩︎
385. Holzel et al, Differential engagement of anterior cingulate and adjacent medial frontal cortex in adept meditators and non-meditators (Neuroscience Letters, 2007) ↩︎
386. Davanger et al, Meditation-Specific Prefrontal Cortical Activation during Acem Meditation: An FMRI Study (Sage Journals, 2010) ↩︎
387. Engstrom, Soderfeldt, Brain Activation During Compassion Meditation: A Case Study (The Journal of Alternative and Complementary Medicine, 2010) ↩︎
388. Brewer et al, Meditation experience is associated with differences in default mode network activity and connectivity (Biological Sciences, 2011) ↩︎
389. Scott, Apologizing Sincerely and Effectively (verywellmind, 2022) ↩︎
390. Libon et al, Neuropsychological deficits associated with Complex
     Regional Pain Syndrome (Journal of the International Neuropsychological Society, 2010) ↩︎
391. Grimm et al, Imbalance between Left and Right Dorsolateral Prefrontal Cortex in Major Depression Is Linked to Negative Emotional Judgment: An fMRI Study in Severe Major Depressive Disorder (Biological Psychiatry, 2008) ↩︎
392. Jones, Graff-Radford, Executive Dysfunction and the Prefrontal Cortex (Behavioral Neurology and Psychiatry, 2021) ↩︎
393. Hiser, Koenigs, The multifaceted role of ventromedial prefrontal cortex in emotion, decision-making, social cognition, and psychopathology (Biological Psychiatry, 2018) ↩︎
394. Suzuki, Tanaka, Functions of the ventromedial prefrontal cortex in emotion regulation under stress (Scientific Reports, 2021) ↩︎
395. Lee et al, Brain Alterations and Neurocognitive Dysfunction in Patients With Complex Regional Pain Syndrome (Journal of Pain, 2015) ↩︎
396. Tajerian et al, Brain Neuroplastic Changes Accompany Anxiety and Memory Deficits in a Model of Complex Regional Pain Syndrome (Pain Medicine, 2014) ↩︎
397. Shokouhi et al, Structural and Functional Brain Changes at Early and Late Stages of Complex Regional Pain Syndrome (Journal of Pain, 2018) ↩︎
398. Michal et al, Association of Neglect-Like Symptoms with Anxiety, Somatization, and Depersonalization in Complex Regional Pain Syndrome (Pain Medicine, 2017) ↩︎
399. Halicka et al, Neuropsychological Changes in Complex Regional Pain Syndrome (CRPS) (Behavioral Neurology, 2020) ↩︎
400. Swart et al, Cortical changes in complex regional pain syndrome (CRPS) (European Journal of Pain, 2012) ↩︎
401. Vittersø et al, Altered updating of bodily and spatial representations after tool-use in complex regional pain syndrome (Pain, 2020) ↩︎
402. Kuttikat et al, Neurocognitive and Neuroplastic Mechanisms of Novel Clinical Signs in CRPS (Frontiers in Cognitive Neuroscience, 2016) ↩︎
403. Cohen et al, Clinical evidence of parietal cortex dysfunction and correlation with extent of allodynia in CRPS type 1 (European Journal of Pain, 2012) ↩︎
404. Halicka et al, Neuropsychological Changes in Complex Regional Pain Syndrome (CRPS) (Behavioral Neurology, 2020) ↩︎
405. Maleki et al, Patterns of spread in complex regional pain syndrome, type I (Pain, 2000) ↩︎
406. Forss et al, Mirror-like spread of chronic pain (Neurology, 2005) ↩︎
407. Cook et al, Spontaneous Spread of Limb Complex Regional Pain Syndrome to the Ipsilateral Face With Ultimate Corneal Abrasion: A Case Report (A&A Practice, 2020) ↩︎
408. Kozin et al, The reflex sympathetic dystrophy syndrome. I. Clinical and histologic studies: evidence for bilaterality, response to corticosteroids and articular involvement (American Journal of Medicine, 1976) ↩︎
409. Radt, Bilateral Reflex Neurovascular Dystrophy Following a Neurosurgical Procedure (Confinia Neurologica, 2007) ↩︎
410. Birley, Goebel, Widespread Pain in Patients with Complex Regional Pain Syndrome (Pain Practice, 2013) ↩︎
411. Martinez-Lavin et al, Complex Regional Pain Syndrome Evolving to Full-Blown Fibromyalgia
     A Proposal of Common Mechanisms (Clinical Rheumatology, 2021) ↩︎
412. van Rijn et al, Spreading of complex regional pain syndrome: not a random process (Journal of Neural Transmission, 2011) ↩︎
413. Hooshmand, Phillips, Various Complications of Complex Regional Pain Syndrome: Stages of CRPS (Neurological Associates Pain Management) ↩︎
414. Cucchiaro et al, Diffuse Complex Regional Pain Syndrome in an Adolescent
     A Novel Treatment Approach (The Clinical Journal of Pain, 2013) ↩︎
415. Shenker et al, Establishing the characteristics for patients with chronic Complex Regional Pain Syndrome: the value of the CRPS-UK Registry (British Journal of Pain, 2014) ↩︎
416. van Rijn et al, Spreading of complex regional pain syndrome: not a random process (Journal of Neural Transmission, 2011) ↩︎
417. Veldman, Goris, Multiple reflex sympathetic dystrophy. Which patients are at risk for developing a recurrence of reflex sympathetic dystrophy in the same or another limb (PAIN, 1996) ↩︎
418. Hooshmand, Phillips, Spread of Complex Regional Pain Syndrome (Neurological Associates Pain Management) ↩︎
419. Mundluru, Saraghi, Anesthetic Management of a Complex Regional Pain Syndrome (CRPS) Patient With Ketamine (Anesthesia Progress, 2020) ↩︎
420. Schwartzman et al, The use of ketamine in complex regional pain syndrome: possible mechanisms (Expert Review of Neurotherapeutics, 2014) ↩︎
421. Asaad, Glass, Perioperative management for patients with complex regional pain syndrome (Pain Management, 2012) ↩︎
422. Schwartzman et al, Ketamine as Adjunctive Anesthesia in Refractory Complex Regional Pain
     Syndrome Patients: A Case Series (Journal of Clinical Case Reports, 2012) ↩︎
423. Himmelseher et al, Ketamine for Perioperative Pain Management (Anesthesiology, 2005) ↩︎
424. Cramer et al, Preemptive analgesia in elective surgery in patients with complex regional pain syndrome: a case report (Journal of Foot and Ankle Surgery, 2000) ↩︎
425. Stubhaug et al, Mapping of punctuate hyperalgesia around a surgical incision demonstrates that ketamine is a powerful suppressor of central sensitization to pain following surgery (Acta Anaesthesiologica Scandinavica, 1997) ↩︎
426. Lavand’homme et al, Intraoperative Epidural Analgesia Combined with Ketamine Provides Effective Preventive Analgesia in Patients Undergoing Major Digestive Surgery (Anesthesiology, 2005) ↩︎
427. Urban et al, Ketamine as an Adjunct to Postoperative Pain Management in Opioid Tolerant Patients After Spinal Fusions: A Prospective Randomized Trial (HSS Journal, 2007) ↩︎
428. Giustra et al, Vitamin C Could Prevent Complex Regional Pain Syndrome Type I in Trauma and Orthopedic Care? A Systematic Review of the Literature and Current Findings (Medical Bulletin of Sisli Etfal Hospital, 2021) ↩︎
429. Zollinger et al, Can vitamin C prevent complex regional pain syndrome in patients with wrist fractures? A randomized, controlled, multicenter dose-response study (Journal of Bone and Joint Surgery, 2007) ↩︎
430. Shibuya et al, Efficacy and Safety of High-dose Vitamin C on Complex Regional Pain Syndrome
     in Extremity Trauma and Surgery Systematic Review and Meta-Analysis (Journal of Foot & Ankle Surgery, 2013) ↩︎
431. Aim et al, Efficacy of vitamin C in preventing complex regional pain syndrome after wrist fracture: A systematic review and meta-analysis (Orthopaedics & Traumatology: Surgery & Research, 2017) ↩︎
432. Hooshmand, Phillips, Spine and the Autonomic Nervous System (Neurological Associates Pain Management, 2009) ↩︎
433. Lee et al, Risk Factors for Suicidal Ideation among Patients with Complex Regional Pain Syndrome (Psychiatry Investigation, 2014) ↩︎
434. Şar, The Many Faces of Dissociation: Opportunities for Innovative Research in Psychiatry (Clinical Psychopharmacology and Neuroscience, 2014) ↩︎
435. Sabater, The Thousand-Yard Stare: The Expression of Trauma (Exploring Your Mind, 2023) ↩︎
436. Boyer et al, Trauma-Related Dissociation and the Dissociative Disorders:
     Neglected Symptoms with Severe Public Health Consequences (Delaware Journal of Public Health, 2022) ↩︎
437. Cernis et al, Dissociation in relation to other mental health conditions: An exploration using network analysis (Journal of Psychiatric Research, 2020) ↩︎
438. Kienle et al, Somatoform dissociation and posttraumatic stress syndrome – two sides of the same medal? A comparison of symptom profiles, trauma history and altered affect regulation between patients with functional neurological symptoms and patients with PTSD (BMC Psychiatry, 2017) ↩︎
439. Bob, Pain, dissociation and subliminal self-representations (Consciousness and Cognition, 2008) ↩︎
440. Lynn et al, Dissociation and Dissociative Disorders Reconsidered: Beyond Sociocognitive and Trauma Models Toward a Transtheoretical Framework (Annual Review of Clinical Psychology, 2022) ↩︎
441. Nijenhuis et al, Trauma-related Structural Dissociation of the Personality (Activas Nervosa Superior, 2017) ↩︎
442. Nijenhuis et al, Phase-Oriented Treatment of Structural Dissociation in Complex Traumatization: Overcoming Trauma-Related Phobias (Journal of Trauma & Dissociation, 2005) ↩︎
443. Poli et al, The integrative process promoted by EMDR in dissociative disorders: neurobiological mechanisms, psychometric tools, and intervention efficacy on the psychological impact of the COVID-19 pandemic (Frontiers in Psychology, 2023) [Has good images on the Structural Dissociation Model] ↩︎
444. Oosterman et al, Autonomic reactivity in relation to attachment and early adversity among foster children (Developmental Psychopathology, 2010) ↩︎
445. Eilert, Buchheim, Attachment-Related Differences in Emotion Regulation in Adults: A Systematic Review on Attachment Representations (Brain Sciences, 2023) ↩︎
446. Decarli et al, Disorganized attachment in adolescence: Emotional and physiological dysregulation during the Friends and Family Interview and a conflict interaction (Development and Psychopathology, 2020) ↩︎
447. Arancibia et al, Neurobiology of Disorganized Attachment: A Review of Primary Studies on Human Beings (Neuroscience Insights, 2023) ↩︎
448. Kidd et al, Examining the association between adult attachment style and cortisol responses to acute stress (Psychoneuroendocrinology, 2011) ↩︎
449. van Hoof et al, Unresolved–disorganized attachment adjusted for a general psychopathology factor associated with atypical amygdala resting-state functional connectivity (European Journal of Psychotraumatology, 2019) ↩︎
450. Spitoni et al, Disorganized Attachment pattern affects the perception of Affective Touch (Scientific Reports, 2020) ↩︎
451. Attachment Styles and Stress Responses (The Attachment Project, 2022) ↩︎
452. Chalavi et al, Abnormal hippocampal morphology in dissociative identity disorder and post‐traumatic stress disorder correlates with childhood trauma and dissociative symptoms (Human Brain Mapping, 2015) ↩︎
453. Olufowote et al, How Can I Become More Secure?: A Grounded Theory of Earning Secure Attachment (Journal of Marital and Family Therapy, 2019) ↩︎
454. Roisman et al, Earned-secure attachment status in retrospect and prospect (Child Development, 2002) ↩︎
455. Grich, Earned secure attachment in young adulthood: Adjustment and relationship satisfaction (Dissertation Abstracts International, 2002) ↩︎
456. Mitchell, Earning a Secure Attachment Style: A Narrative of Personality Change in Adulthood (Dissertation Abstracts International, 2007) ↩︎
457. Earned Secure Attachment: Transforming Your Insecure Attachment Style (The Attachment Project, 2022) ↩︎
458. Demystifying Dissociation: Principles, Best Practices, and Clinical Approaches (NetCE trchealthcare) ↩︎

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