Complex Regional Pain Syndrome (CRPS)

Ross Hauser, MD

If you are reading this article and you have been diagnosed with Complex Regional Pain Syndrome (CRPS) you are probably looking for some possible answers to help you. You do not need a lecture on what painkillers are doing to your body, painkillers may be the only way you are getting through each day. You know painkillers are probably bad for you, but what other recourse do you have when nothing else has worked?

Because you are here reading this article it is likely you have been diagnosed with Complex Regional Pain Syndrome or a loved one has. You may be the “typical case” of extreme chronic pain in the arms and legs, or you may be the more challenging case where a migraine is present and you may have hearing problems, visual disturbances, and other neurological-like symptoms. You may have a long history of inflammatory or rheumatoid arthritis and fibromyalgia.

This article is part of a series. Please see Complex Regional Pain Syndrome following multiple knee surgeries and knee replacement.

Discussion points of this article:

Part 1: Diagnosis of CRPS

PART 2 – TREATMENTS FOR CRPS

Part 3: Ligament instability: Addressing immobilization and ligament structural damage. Is this an “unknown” cause of Complex Regional Pain Syndrome?

Complex regional pain syndrome is a complex and often poorly understood condition

Stages of CRPS

CRPS is a deteriorating disease and progresses in three stages.

Many doctors believe that Complex regional pain syndrome is a lack of or confused communication between the immune system, the inflammatory response, and the nervous system.  These include the sympathetic nervous system (responsible for getting the muscles ready for intense physical activity), the somatomotor system (coordination and balance), the neuroendocrine systems (metabolism, energy, heart rate), the nociceptive system (our body’s response mechanism to threat or harmful stimulus), as well as an inflammatory response.

CRPS-I is more mysterious as it occurs without obvious or confirmed nerve injury.

Your doctor or doctors may have explained to you that CRPS is divided into two types. CRPS-I and CRPS-II. CRPS-I is more mysterious as it occurs without obvious or confirmed nerve injury.  CRPS-II is when nerve injury can be documented. A disease that has no obvious cause is a disease that is difficult to treat. This is demonstrated by a June 2021 paper, led by researchers at the University of Arizona College of Medicine-Phoenix, and published in the journal Pain and Therapy (1):

“Treatment modalities available range from physical therapy, pharmacotherapy, and interventional techniques. Physical and occupational therapies include mirror therapy (briefly, if your left leg has extreme pain, you trick and retrain the brain, by use of a mirror to see your reflected image right leg as your left leg, and you “show” your brain that you can move the limb without pain and restriction).

Medical management with non-steroidal anti-inflammatory drugs (NSAIDs) has not shown significant improvement.

There have been supporting findings in the use of short-course steroids, bisphosphonates (generally given for bone loss), gabapentin (seizure medication), and ketamine (for pain). Antioxidant treatment has also shown some promise. (Below we will further discuss these options). Other pharmacotherapies include low-dose naltrexone and Botulinum toxin A (BTX-A). Sympathetic blocks are routinely used, even if their short- and long-term effects are not clear. Finally, spinal cord stimulation (SCS) has been used for decades.”

If you are a loved one or caregiver of someone diagnosed with complex regional pain syndrome you are probably searching for information because the remedies and treatments listed above may not have been effective for you and you are seeking other answers. We hope this article will provide some insight into possibly helping you or them wean off medications by addressing the underlying cause of the CRPS which may be damaged spinal and joint ligaments allowing for hypermobility which in turn turns into hypersensitivity and sensory disturbance.

More on the different types of complex regional pain syndrome

Many people who contact our center will often tell us that they have a classification of the type of complex regional pain syndrome they have. Some of these people, do not truly understand what their type means. I also point out that many people that contact us do not even discuss a “Type.”

From injury or post-surgical complication to CRPS. The long journey of seeking help

People who contact our center will usually describe the injury that caused their complex regional pain syndrome to develop first. The CRPS will usually be discussed as secondary until they start discussing their pain.

From injury or post-surgery to CRPS

It started with a partial Achilles tear, and from there it developed into chronic Achilles tendinopathy. Then it developed into neuropathy and from there CRPS. Can you help?

I was in an accident where I suffered numerous fractures in my leg. I have now been diagnosed with Complex Regional Pain Syndrome. My doctors said there is no cure. I am not looking for a cure, I am only looking for some alleviation of the burning pain.

I had spinal surgery that did not help and was then diagnosed with “Failed Back Surgery Syndrome.” My pain became worse and I had a spinal cord stimulator implanted.

I had a meniscus and arthroscopic surgery. Three months later my knee is very painful, with limited mobility, and the loss of muscle is very noticeable. I am now off medication for “nerve damage.” If you developed CRPS after knee surgery, please see our article: For more specific information please see our article Complex Regional Pain Syndrome following multiple knee surgeries.

I was diagnosed with Complex Regional Pain Syndrome after receiving a cortisone shot. I suffer from gastric pain, reflux, dizziness, low blood pressure, increased heart rate, constipation, occasional diarrhea, nausea, migraines, neck pain, upper back pain, hoarseness, sound sensitivity, and arrhythmia.

Like the sample stories above, complex regional pain syndrome (CRPS) generally develops following a physical injury, it is disproportionate pain sensation (too much pain) to the precipitating event or level of tissue damage (the injury that causes it). An acute description of this problem may be one that describes it as “spreading like wildfire,” perhaps starting in the foot, moving its way up to the knee and back, then down the other leg, and up into the arms.

The patient’s poor understanding of CRPS was associated with greater disability and fear of movement

Different diagnostic terms for CRPS

The various diagnostic terms referring to CRPS

Complex regional pain syndrome is a complex and often poorly understood condition

A February 2021 study (3) in the journal Pain Medicine comes from The University of Auckland in New Zealand that helps put scientific reality into the cause of helping patients, doctors, and families understand Complex Regional Pain Syndrome. Here are the highlights of this research.

Complex regional pain syndrome is a complex and often poorly understood condition, and people with CRPS will have diverse beliefs about their symptoms. According to the self-regulation model (the self-regulation model is described as a means to measure how people try to understand their illness or disease. They want to know what caused it, and what are the short-term and long-term treatments or management of the disease. They want to know if it can be cured or managed), and these beliefs (termed “illness perceptions”) influence health behaviors and outcomes.

In other words, the impact of having Complex Regional Pain Syndrome and not understanding the disease may lead to poor decision-making in regard to treatment.

The study’s findings of how a group of people with Complex regional pain syndrome reacted to their diagnosis and symptoms:

So what does this mean?

Researchers are helping you identify issues you are facing so someone may believe you. This agrees with our own clinical observations and decades of care in helping people with Complex Regional Pain Syndrome, a large part of the battle is getting someone to believe you and you believe something can be done to help based on your own understanding of what Complex Regional Pain Syndrome is.

 

The migraine headache – “CRPS of the brain” – is this a diagnostic tool?

One of the challenges patients with CRPS face is a true diagnosis. Many patients, such as yourself, have spent years trying to get a diagnosis so they can get some type of treatment that may help. The problem currently is a lack of understanding criteria for making a diagnosis or that doctors are even aware enough that this criterion even exists. In this section, we will review an understanding of the diagnostic criteria for CRPS and then introduce research concerning migraines. Migraine headache is a frequent problem we see in CRPS and cervical spine instability patients. Migraine may be the missing link to understanding the treatment of CRPS.

Researchers and doctors have tried to come up with diagnostic criteria for CRPS. Currently, the most widely accepted clinical diagnostic criteria are the Budapest criteria. If you are reading this article and have been diagnosed with CRPS, it was likely based on this checklist of symptoms: (This criteria appears in the appendix of a review article from researchers in the United Kingdom. “A randomized placebo-controlled Phase III multi-center trial: low-dose intravenous immunoglobulin treatment for long-standing Complex Regional Pain Syndrome (LIPS trial).”(4)

Let’s pause here for an explanatory note: 

We often see patients with a very heightened sensitivity to pain, especially the skin. A cool breeze will “burn,” exposed skin. Bed sheets will cause a similar pain sensation when they try to sleep. Updated information in the National Center for Biotechnology Information publication STAT PEARLS (5) offers this explanation and understanding of hyperaesthesia and allodynia.

“The official International Association for the Study of Pain definition of allodynia at the time of this article is “pain due to a stimulus that does not normally provoke pain.” An example would be a light feather touch (that should only produce sensation) causing pain. Allodynia is different from hyperalgesia, which is an exaggerated response from a normally painful stimulus, although both can and often do co-exist. Both are types of neuropathic pain.

An example of the difference between allodynia and hyperalgesia on the physical exam would be softly rubbing a cotton-tipped swab against a patient’s skin. Lightly brushing a swab against the skin would cause a low-level stimulus, but should not elicit a pain response. A patient who experiences pain with a stimulus that should only cause sensation may have allodynia. If the clinician significantly increases the degree of pressure, some pain would be part of a normal response. A patient who feels an excessive amount of pain would be noted to have hyperalgesia.”

Returning to the criteria: The patient must display at least one sign at the time of evaluation in two or more of the following categories:

Must display at least one sign at the time of evaluation in two or more of the following categories:

Migraine and complex regional pain syndrome

Research led by the Stanford Headache and Facial Pain Program, Department of Neurology and Neurological Sciences, Stanford University School of Medicine (6) made these observations in connecting migraine headaches and the risk of development of CRPS:

“Migraine is significantly associated with CRPS, prompting some authors to call migraine as “CRPS of the brain” whereas other experts coined the term “migrainous corpalgia” (simply translated as migraine causing chest and body pain), to suggest shared pathophysiology of central sensitization between the two conditions while describing migraine’s cephalic (symptoms related to the head) and extracephalic cutaneous allodynic presentations (simply the pain in your skin outside your head region).

Migraine and CRPS have shared pathogenetic backgrounds (the causes of both problems have common links). Neuropeptides such as CGRP (or Calcitonin gene-related peptide are highly potent vasodilators (responsible for blood flow and circulation). Disruption of blood flow to the brain can result in the well know symptoms of dizziness, brain fog or concentration problems, vision problems, migraines, mast cells, neurogenic inflammation, and reactive oxygen species (ROS) are involved in both migraine and CRPS.

Learning points at a glance:

Triggers for CRPS included fall injuries (41%), postsurgical wounds (41%), fractures (8%), motor vehicle accidents (5%), idiopathic causes (3%), and others (3%). Among all 150 patients, past or present psychological comorbidities included depression disorder (49%), anxiety disorder (36%), bipolar disorder (9%), and posttraumatic stress disorder (6%)

We are going to come back and revisit the idea of disruption of blood flow to the brain later in this article.

Patients with Complex Regional Pain Syndrome will face significant quality-of-life consequences

Patients with CRPS will face significant quality-of-life consequences as this pain syndrome dramatically alters their lives as well as the lives of their families and friends. In 2000, noted researcher Bradley S. Galer of the Department of Pain Medicine and Palliative Care, Beth Israel Medical Center in New York wrote in the Journal of Pain and Symptom Management (7) that a majority of patients felt that symptoms of CRPS caused “substantial interference” with general activities (74%), mood (74.2%), mobility (67.7%), normal work (74.2%), relations (64.5%), sleep (67.7%), and social activities (74.2%). Interference in self-care was identified in 45.2%. This study also noted the average duration of CRPS in the 31 patients surveyed to be 3.3 years. The need to use a device, such as a cane, walker, or wheelchair, was reported by 35% of the participants.

Over twenty years later, little as far as progress was seen. Building on this research, a July 2022 paper in the European Journal of Pain (8) examined previous research on the quality of life impact of CRPS patients and found:

Circulatory problems and constricted blood vessels and exaggerated neurogenic inflammation 

Many doctors believe that Complex Regional Pain Syndrome is a lack of or confused communication between the immune system, the inflammatory response, and the nervous system.  These include the sympathetic nervous system (responsible for getting the muscles ready for intense physical activity), the somatomotor system (coordination and balance), the neuroendocrine systems (metabolism, energy, heart rate), the nociceptive system (our body’s response mechanism to threat or harmful stimulus), as well as an inflammatory response. This is discussed below.

In 2010 Caring Medical’s Ross Hauser, MD, published “The Theoretical Basis for and Treatment of Complex Regional Pain Syndrome with Prolotherapy.” In this paper, he presented treatment guidelines for helping patients with simple dextrose injections into painful areas. The highlights and learning points of this paper are presented here with research updates into 2020. This will also be discussed below.

The autonomic nervous system response

Looking for answers to Complex Regional Pain Syndrome can lead the sufferer in many different directions. A study from 2008 (9) sought to help provide insight into the nervous system. The paper notes: Complex Regional Pain Syndrome is chronic pain and potentially disabling syndrome which typically affects the extremities. It is characterized by a variety of autonomic (involuntary or unconscious autonomic nervous system response), and vasomotor disturbances, of which diffuse pain, spreading edema, temperature disturbances, and functional impairment are most prominent.

In 2010, noted researcher Professor Gunnar Wasner MD wrote in the journal Pain Medicine (10)

Circulatory problems and constricted blood vessels and exaggerated neurogenic inflammation 

Driven by peripheral mechanisms or peripheral nerve disorders

Explanatory note: peripheral nerve disorders

When there is a dysfunction in the peripheral nerve system. 

For many of you, this may be a moment of understanding, for others, this is something you have already been told. Our attempt here is a simple understanding of why you have this pain. When there is a dysfunction in the peripheral nerve system, systems may include:

When there is a dysfunction in the peripheral nerve system what can be impacted? Where does it make you hurt?

The peripheral nervous system connects sensations and messages between the brain and spinal cord with the limbs and organs. In your previous doctor visits, it may have been explained to you that the peripheral nervous system is made up of nerves and ganglia (nerve relay stations) outside the brain and spinal cord. It is a nerve network that ultimately connects to the brain. Here is a simple explanation of where dysfunction in the peripheral nervous system may be hurting you.

Why do CRPS patients have vision problems?

People with CRPS, probably like yourself, have primary symptoms, secondary symptoms, and symptoms that “get lost,” in the myriad of other symptoms. One of these symptoms may be visual disturbances. Visual disturbance is a problem we often see in patients with cervical spine and neck instability. Please see our article Chronic Neck Pain and Blurred or Double Vision Problems for a more detailed discussion.

In the October 2020 issue of the journal Pain (11), researchers examined the possible causes of visual disturbances in CRPS. In Complex Regional Pain Syndrome (CRPS), hyperalgesia encompasses uninjured sites on the ipsilateral (the same side) side of the body and may also include the special senses, as auditory discomfort often is greater on the CRPS-affected side. To determine whether this Hemi-lateral (the same side) hyperalgesia involves the visual system, the discomfort threshold to a light source was investigated for each eye, and the nasal and temporal half of each visual field, in 33 patients with CRPS and 21 pain-free controls.

What the researchers found was ipsilateral photophobia (same side light sensitivity and visual discomfort) was associated with mechanical (touch movement sensitivity) and thermal (temperature-sensitive) hyperalgesia of the patient’s forehead, but the vision problems were not worsened when the limbs were exposed to the touch of hot-cold sensation.

The researchers of this study concluded: “Together, these findings suggest that aberrant processing of nociceptive (the process of pain perception) input in the ipsilateral trigeminal-medullary region of the brainstem contributes to visual discomfort in CRPS.”

In our article, The Evidence for Trigeminal Neuralgia Non-Surgical Treatments, we suggest Trigeminal neuralgia centers on what is happening to the trigeminal nerve which carries pain, feeling, and sensation from the brain to the skin of the face. In the case of trigeminal neuralgia, most medical professionals cannot find the cause of why this pain started. This is borne out by the definition of trigeminal neuralgia. We suggest an understanding and diagnosis of possible trigeminal nerve compression. This is something we would also understand to possibly contribute to Complex Regional Pain Syndrome in some patients.

PART 2 – TREATMENTS

A June 2023 paper in The Cochrane Database of Systematic Reviews (12) writes: “There is currently no consensus regarding the optimal management of CRPS, although a broad range of interventions have been described and are commonly used. Despite a considerable increase in included evidence (recently), we identified no high-certainty evidence for the effectiveness of any therapy for CRPS. A study from the Trauma & Orthopaedic Department, Oxford Trauma Unit, John Radcliffe Hospital in Oxford, UK offered these 2023 treatment guideline suggestions (7): There is strong evidence to suggest the efficacy of prompt physiotherapy, lidocaine, ketamine, bisphosphonates (a class of drugs sometimes given to relieve pain in bone cancer patients), sympathectomy (cutting or burning of the nerve path) and brachial plexus blocks (for main relief in the shoulder region) in the management of CRPS. . . . “

The role of anti-inflammatory medications and painkillers

Prednisolone

For many people with CRPS, over-the-counter or prescription non-steroidal anti-inflammatory drugs (NSAIDs) will be tried as an initial treatment. If the CRPS does not resolve, stronger anti-inflammatories may be prescribed. One such medication is prednisolone, a corticosteroid. A July 2023 paper in the Journal of clinical neuroscience (13) compared the effectiveness and safety of prednisolone 20 mg versus 40 mg in CRPS-I patients. The researchers of this study looked at 50 CRPS-I of shoulder joint patients. Patients were randomized to prednisolone 40 mg/day (group I) or 20 mg/day (group II) for 14 days, then tapered to 10 mg in group I and to 5 mg in group II by 1 month. Both groups received prednisolone 5 mg/day for 2 months.

At one month, all 50 patients had more than a 50% pain reduction as measured by the 0-10 Visual Analogue Scale (VAS, 10 being the worst pain). The difference however between the higher dose prednisolone and the lower dose prednisolone was insignificant. The researchers suggested prednisolone 20 mg was as effective as 40 mg in CRPS-I and is safe in diabetic patients.

TNF-α inhibitors, intravenous infliximab

A June 2023 paper (14) examined treatment with three sessions of 5 mg/kg intravenous infliximab in 15 patients.  Infliximab is a TNF-α (inflammation inhibitor.) Eleven patients (73.3%) were categorized as responders with a positive treatment effect. Treatment frequency is every four to six weeks.  One patient described side effects such as itching and rash. Let’s look further at TNF-a inhibitors and inflammation.

A June 2020 study in the journal Pain and Therapy (15) offers suggestions for understanding inflammation in CRPS patients. The researchers of this study noted that other studies have found higher levels of proinflammatory cytokines (these are immune system messenger cells that send chemical signals to create more inflammation) in blister fluid in the form of tumor necrosis factor-alpha (TNFα) of the affected extremity compared with the unaffected extremity, and this could suggest a role for local inflammatory processes in CRPS.

Our explanatory note: Tumor-Necrosis factor (TNFα) is a cell-signaling protein (cytokine), which communicates commands to create inflammation such as in chronic joint swelling. The idea is if you can block TNFα and other inflammatory factor production or at least inhibit it, joint swelling will be reduced, and hopefully, the amount of articular cartilage breakdown resulting from a toxic, over-inflamed joint environment will be slowed.

The researchers also noted elevated levels of proinflammatory cytokines having also been found in the serum, plasma, and cerebrospinal fluid of patients with CRPS, which may be involved in peripheral nociceptor activation and sensitization.

Low-Dose Naltrexone

Naltrexone is a drug to help with drug and alcohol dependency. In lower doses, research suggests it may offer pain relief. A June 2023 study (16) from Emory University researchers examined the use of Low-Dose Naltrexone (LDN) for chronic pain. They write: Low-dose naltrexone (LDN) has increased in popularity as a non-opioid medication that may decrease chronic pain symptoms. Low-Dose Naltrexone is most commonly used to treat fibromyalgia, complex regional pain syndrome (CRPS), and painful diabetic neuropathy.

Botulinum toxin and nerve blocks for Complex Regional Pain Syndrome type 1

A December 2021 study in Anesthesiology (17) tested the hypothesis that botulinum toxin would prolong the duration of a lumbar sympathetic block measured through a sustained increase in skin temperature. Of a total of 48 patients, 24 would get the botulinum toxin and 24 would get the placebo and were randomly assigned. The change in relative temperature increase was higher in the botulinum toxin group than in the control group which was maintained at three months. Further, the researchers found, the pain intensity was greatly reduced in the botulinum toxin group compared with the control group at one month and three months. They concluded that in patients with complex regional pain syndrome, lumbar sympathetic ganglion block using botulinum toxin type A increased the temperature of the affected foot for three months and also reduced the pain.

Topical capsaicin controversy surrounding functional

A January 2023 case study in the journal Cureus (18) reported the case of a female patient with CRPS type II, whose treatment with topical capsaicin resulted in great functional improvement. Here is what they recorded: “The patient was referred to the Pain Medicine Unit due to a CRPS type II due to trauma in her right wrist. She complained of severe pain in the median nerve territory of her dominant hand, associated with hyperalgesia, allodynia, burning, and electric shock sensation, resulting in functional disability. Electromyography was compatible with severe axonal injury of the right median nerve of the wrist. After conventional therapies were tried with no improvement, treatment with a capsaicin 8% patch was proposed. A functional improvement was observed after two applications of the capsaicin treatment, allowing the patient to regain activity in her hand.” This was one case but the attending doctors thought is significant enough to document in a medical journal with the conclusion: ” This shows that although evidence for capsaicin use in CRPS treatment is scarce, it can be a viable alternative for some patients.”

Anticonvulsants and antidepressants for Complex Regional Pain Syndrome

November 2020 research from the University of Texas published in the journal Pain Management (19) offered this on the use of anticonvulsants and antidepressants in CRPS.

Anticonvulsants and antidepressants are commonly prescribed for neuropathic pain conditions; however, evidence is sparse on whether these drugs are effective in reducing CRPS-related pain. . . Overall, evidence (published research) is considered insufficient for the use of gabapentinoids for CRPS-related pain. However, (some studies) did find gabapentin to result in significant improvement in pain whereas one (study) reported the use of amitriptyline (antidepressant and nerve pain medication) to be equally as effective as gabapentin. Multiple case reports discussing the efficacy of pregabalin in pediatric CRPS patients, with relatively short duration of disease and underlying psychiatric illness, have been reported, but these findings need to be validated.”

Electrical Stimulation for Complex Regional Pain Syndrome

Above we had an example of someone who contacted us who had spinal surgery that did not help and was then diagnosed with “Failed Back Surgery Syndrome.” Their pain became worse and they had a spinal cord stimulator implanted. This did not help them either. Some people do get great benefits from spinal cord stimulators. These are not the people we typically see at our center. We see the failures. However, people as noted in this study can find alleviation of pain with electrical stimulators.

In November 2020, researchers publishing in the journal Case Reports Neuromodulation (20) examined Direct Sciatic Nerve Electrical Stimulation for Complex Regional Pain Syndrome Type 1. In fact, that was the name of the paper. Here are their findings:

Does oral vitamin C supplementation help prevent incidences of Complex Regional Pain Syndrome?

The concept behind vitamin C oral supplementation is that it can help fight off oxidative stress and work as an anti-inflammatory and tissue regenerator. However, there is still a lot of debate as to how vitamin C actually works in preventing Complex Regional Pain Syndrome, and some debate if it works at all. The research below gives endorsement to oral supplementation of 500 – 1000 mg for a period of 40 – 50 days post-surgery.

Distal radius, wrist, foot, and ankle surgeries

In August 2022, doctors writing in The Journal of Foot and Ankle Surgery (21) examined the effect of pre-surgery Vitamin C doses on the incidence of Complex Regional Pain Syndrome. In this study, the doctors noted: Controversy exists regarding the effectiveness of vitamin C in reducing the incidence of complex regional pain syndrome. To help add science to the controversy the doctors and researchers conducted this systematic review and meta-analysis of past published data to better assess the preventive role of vitamin C on CRPS-I and functional outcomes after distal radius, wrist, foot, and ankle surgeries.

Data taken from eight studies were included. The average time frame for vitamin C administration in each study ranged from 42 to 50 days post-injury and/or surgical fixation. Vitamin C dose was 500 mg or 1000 mg.)

Foot and ankle surgery

In September 2021, doctors writing in the journal International Orthopaedics (22) looked for answers to help people who develop complex regional pain syndrome after foot and ankle surgery which impacted their ability to walk. Here is what they wrote: “As the symptomatic treatment of this disaster complication is poor and has low efficacy, a preventive treatment would be beneficial. Vitamin C has been reported to be efficient in preventing CRPS in elective scheduled surgery.” In their study among the 329 patients included (232 women and 97 men), 121 patients were included in the vitamin C group and 208 in the control group (without vitamin C).

Subacromial shoulder surgery

Results: Taking 1000 mg (1 g)  per day of vitamin C for 40 days after a foot or ankle surgery reduces the risk of CRPS. In the same group, alcoholism and cast immobilization were increased risk factors for CRPS.

A February 2020 study in the European Journal of Orthopaedic Surgery & Traumatology (23) looked to see if  oral vitamin C reduced the incidence of CRPS-I after subacromial shoulder surgery

A group of 542 patients who had subacromial shoulder surgery was divided into two groups. One group received no vitamin C the other group received (500 mg/day of oral vitamin C for 50 days postoperatively). The relationship between vitamin C administration and the development of CRPS-I was assessed.

Part 3: Ligament instability

Addressing immobilization and ligament structural damage. Is this an “unknown” cause of Complex Regional Pain Syndrome?

Types of cervical ligament injuries

In this section, I will delve into an “unknown,” possibility to the cause of CRPS. Ligament laxity. A condition of weakened or lax ligaments. A condition that can be repaired. The basis of this section is our 2010 article “The Theoretical Basis for and Treatment of Complex Regional Pain Syndrome with Prolotherapy,” with updated information for 2023.

Following the path of CRPS through ligament damage

CRPS generally appears following physical trauma, involving the bone and soft tissues which are treated with long periods of immobility. While this immobility itself may be needed to heal a bone injury such as a fracture, it encourages ligament injuries not to heal. Stress deprivation or immobility causes a protracted state of progressive atrophy and a lack of mechanical strength in the injured ligaments.

Learning points:

Prolonged immobilization, loss of motion

 Perhaps it is the failed ligament healing that is responsible for the chronic signs and symptoms of CRPS.

It is easy to assume that when a person is subjected to a force significant enough to fracture a bone, ligaments close to the fracture site would also be injured. The immobilization that follows, induces destructive changes in the joint, which itself could be painful. Once the cast is removed, for instance, the patient has numerous causes for pain including joint or muscle contractures, as well as failed ligament healing, though the fracture itself healed. Perhaps it is the failed ligament healing that is responsible for the chronic signs and symptoms of CRPS.

The nerve endings in ligaments and their impact on Complex Regional Pain Syndrome

The high density of both myelinated (insulated nerve endings that move pain sensation quickly) and unmyelinated nociceptors (uninsulated nerve endings that move sensation of pain more slowly) in the non-healed ligaments then become sensitized to the point that even normal or less than normal activities activate them to fire causing severe burning pain.

These activated nociceptors through local and feedback loops in the central nervous system, cause the autonomic phenomenon in the extremity including referral pain, edema, and temperature disturbances.

In a case reported in the medical literature, immobilization of the ankle leads to CRPS

A 2019 paper (24)  in the Journal of Orthopedic Case Reports presented a case at King Edward Memorial Hospital. Here are the learning points:

Impaired Pain Processing at a Brainstem Level in Patients with Chronic Complex Regional Pain Syndrome

In December 2022, doctors at the Department of Neurology, University Medicine Greifswald in Germany, published findings on impaired pain processing at the brainstem level. This research appeared in the International Journal of Molecular Sciences. (25) Here is the summary of this research:

Neuroinflammatory mechanisms and maladaptive neuroplasticity (disruption of normal brain function, pain either causes chronic stress, anxiety, and depression or chronic stress, anxiety, and depression causes chronic pain) underlie the progression of complex regional pain syndrome (CRPS), which is prototypical of central neuropathic pain conditions. (The familiar symptoms to CRPS patients of temperature dysregulation – being uncomfortably hot or cold, stabbing, shooting, burning pain, numbness – tingling sensation). What the researchers of this study wanted to know is if these symptoms could be caused by problems in the brainstem. (Please see my article for the vast array of symptoms that could be caused by brainstem compression – Problems of Compression of the brainstem – Atlantoaxial instability and Atlas displacement.) In this study, the researchers looked at pain-modulatory brainstem pathways in CRPS using the nociceptive blink reflex (nBR). The nociceptive blink reflex is a test as it sounds to test for the blink reflex and pain and dysfunction along the trigeminal and the facial (VII) nerve. A “bad” result would be dysfunction in these nerves’ ability to generate a blink showing a neurological decline in the muscles that make the eye blink.

What happened in this study was a “deficient habituation” or reduced reaction to the stimulation was a point of high interest to the researchers since “a reduced habituation response of the blink reflex has been reported in patients with migraine and is thought to generally reflect impaired information processing between the brainstem, thalamus, and higher cortical areas.” This could demonstrate “disinhibition (simply the inability to manage a “rogue” behavior as in sensing too much pain) as a source of increased brainstem excitability to painful stimulation remote from the limb directly affected by CRPS, further support actual pathophysiological concepts in neuropathic pain. Here, impaired central information processing, altered excitability, and mechanisms of disinhibition of brainstem pain-modulation circuits are thought to result in a pro-nociceptive state, contributing to a reduced analgesic ability (ability to manage pain) and an increased sensitivity to incoming somatosensory stimuli (hypersensitivity to pain).

Brain stem compression and cervical spine instability

For many of the neurologic, vascular, and psychiatric-like problems we see, there is an issue with possible compression of the brainstem / spinal cord. In the illustration below we see clearly that the brainstem and spinal cord slip neatly into the space provided by the proper alignment of the C1-C2 atlas/axis. The key here is a properly aligned C1-C2.

What are we seeing in this image?

In this illustration, we demonstrate the blockage of cerebrospinal fluid caused by upper cervical spine instability and problems in the neck. This blockage can lead to the increase of inflammatory factors in the cerebrospinal fluid and create some of the problems of Complex Regional Pain Syndrome-related dystonia and other neurological symptoms possibly including pain intensity.

In this illustration we demonstrate the blockage of cerebrospinal fluid caused by upper cervical spine instability and problems in the neck. This blockage can lead to the increase of inflammatory factors in the cerebrospinal fluid and create some of the problems of complex regional pain syndrome-related dystonia and other neurological symptoms possibly including pain intensity.

Our explanatory note: Cerebrospinal fluid (CSF) is critical to ensuring the removal of waste products from the brain through the brain’s lymphatic system. Metabolic waste products from the neurons flow into the CSF and are removed into the brain’s lymphatic system (lymphatic system.)

Complex Regional Pain Syndrome-related dystonia and inflammation in the cerebrospinal fluid

Many of you reading this article may have a secondary diagnosis of Complex Regional Pain Syndrome-related dystonia. Researchers recently made a connection between inflammation as measured in the cerebrospinal fluid and the development of involuntary muscle movement.

A 2014 study (23) led by Dutch researchers at Leiden University Medical Center suggested a connection between Complex Regional Pain Syndrome (CRPS)-related dystonia and “compelling evidence (that) points to the involvement of the central nervous system. The researchers applied an exploratory metabolomics analysis (as the name implies a study of how the data is collected to see if they can uncover new information in identifying the cause of this medical problem) of cerebrospinal fluid (CSF) of patients with CRPS-related dystonia. What the researchers said was that using this new data model, they could better isolate a “metabolic signature,” in the cerebrospinal fluid in which inflammatory factors were leading to a catabolic state (cell breakdown) in chronic CRPS patients with dystonia that is likely associated with inflammation as seen in the cerebrospinal fluid.

Prolotherapy treatments for Complex Regional Pain Syndrome

Prolotherapy is a simple, non-surgical, in-office, injection treatment that stimulates the body’s immune system to repair painful joints.

Prolotherapy is considered an alternative treatment for:

The basic concept of Prolotherapy is simple. A proliferant (something that awakens and ignites the immune system’s healing process) is injected into damaged joints and spinal ligaments or tendons, which leads to local inflammation. Prolotherapy will be used to heal soft tissue damage such as ligament injury. Prolotherapy involves injections at the site of the damaged ligament. This will initiate a local inflammatory response which will encourage blood to flow to the injured site.

Research by George S. Hackett, M.D., who coined the term Prolotherapy, found that ligament relaxation (his term for non-healed ligament injuries) caused bone dystrophy (osteopenia/osteoporosis), which is a common feature of CRPS. He also noted that ligament relaxation often activated the sympathetic nervous system and that when Prolotherapy was performed on the injured ligament(s), not only did the local pain remit but so did the autonomic phenomenon. Since traditional treatments do not address non-healed ligament injuries, this entity could be the reason that so many cases of CRPS are never resolved. Since Prolotherapy causes ligament regeneration, it should be in the arsenal of any clinician treating patients with unresolved CRPS symptoms.

Treating migraines that have been unresponsive to other treatments by treating cervical spine instability. Could this be an answer?

In this section, we will continue with the evidence that makes a connection between treating migraines and possibly CRPS by addressing concerns in the cervical spine and the generation of body-wide pain that may be coming from the neck. The above researchers used the term “migrainous corpalgia” (migraine causing chest and body pain), so here we present a possible solution: Treating migraines that have been unresponsive to other treatments by treating cervical spine instability. Could this be an answer?

Treatments that do not work, do not work because they do not address the problems of cervical spine instability from cervical ligament damage.

Among some of the reasons that patients do not get a headache or migraine relief is that pharmaceutical-based management of the patient’s headaches does not address the problem of headaches coming from neck pain caused by weakened or damaged cervical ligaments.

In our 2014 research led by Danielle R. Steilen-Matias, MMS, PA-C, and published in The Open Orthopaedics Journal (24) our research team was able to demonstrate that when the neck ligaments are injured, they become elongated and loose, which causes excessive movement of the cervical vertebrae. In the upper cervical spine (C0-C2), this can cause a number of other symptoms including, but not limited to, nerve irritation and vertebrobasilar insufficiency with associated vertigo, tinnitus, dizziness, facial pain, arm pain, and migraine headaches.

A brief note on vertebrobasilar insufficiency. Typically this describes a narrowing of the arteries that is usually treated with blood thinners and cholesterol medication. In this context, vertebrobasilar insufficiency is describing a situation where hypermobility of the neck vertebrae is causing a “squeezing,” of the arteries by pinching movement.

Our research was cited in an April 2018 study in the International Journal of Environmental Research and Public Health. (25) Here researchers wrote:

Occipital allodynia (a super sensitivity to pain)

“Emerging evidence of occipital nerve compression in unremitting head and neck pain.” That is the title of recent research that appears in the July 2019 issue of The Journal of Headache and Pain (26) It comes from researchers at the University of Texas and Harvard Medical School.

The cause of unremitting head and neck pain in some patients may be compression of the lesser and greater occipital nerves by the posterior cervical muscles and their fascial attachments at the occipital ridge (where the base of the skull meets the spine) with subsequent local perineural inflammation (nerve inflammation). The resulting pain is typically in the sub-occipital and occipital location, and, via anatomic connections between extracranial and intracranial nerves, may radiate frontally to trigeminal-innervated areas of the head. Migraine-like features of photophobia (light sensitivity) and nausea may occur with frontal radiation.

The researchers suggest extracranially-directed treatments such as occipital nerve blocks, cervical trigger point injections, botulinum toxin, and monoclonal antibodies may provide more substantial relief for unremitting head and neck pain; additionally, decompression of the occipital nerves from muscular and fascial compression is effective for some patients and may result in enduring pain relief.

Temperature dysfunction problems & CRPS associated with nerve compression & spinal cord tension

In the video below, and the extensive article on our site: Thermoregulatory instability – Neck pain and inability to maintain consistent body temperature, we discuss the problem of skin and body temperature in a patient suffering from ailments including Complex Regional Pain Syndrome (CRPS)

Thermoregulatory dysfunction is a problem that its name well describes. The person who has it cannot maintain proper body core temperature. For some people when they are exposed to the cold, their body gets very cold. When they are exposed to heat, they can get very hot, or conversely, get cold. Sometimes the person gets hot or cold without an apparent external stimulating factor. In simplest terms, this person’s thermostat is broken. In the world of a cervical spine specialist who deals with people with chronic, years of ongoing neurologic-type symptoms that may reveal themselves as temperature instability, we have to look at chronic hypothalamic mis-messaging, pathologic changes in cerebral blood flow (the patient does not get enough blood to the brain), metabolic derangement (chemical imbalance often brought on by prolonged opioid use), and a neurogenic inflammatory response (nerve inflammation – something, like a disc or vertebrae is pinching the nerve).

Summary and contact us. Can we help you?

The same principles apply to resolving bizarre neurological conditions or symptoms, as it does to more traditional osteoarthritis pain complaints. Find the ligament injury to resolve the condition. When someone has local autonomic hyperactivity symptoms of the foot (i.e. the patient has a very cold foot compared to the other foot) we determine which ligaments are injured in that foot and then treat them with Prolotherapy. Generally, after 3-6 Prolotherapy sessions, the pain, and the sympathetic symptoms are resolved.

If the condition has persisted for a long time and spread out to involve the other limb, a more comprehensive approach to resolve the conditions is needed. By this time, there will be many “stressors” the person has to overcome including hopelessness, financial burdens, relationship issues, and, of course, the devastating effect of CRPS on the body. In this instance, realistically the person probably needs therapy directed at their whole person; body, soul, and spirit. As much as they allow us to, we will help.

We hope you found this article informative and that it helped answer many of the questions you may have surrounding your CRPS challenges.  If you would like to get more information please email us: Get help and information from our Caring Medical staff

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References


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