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 neurotological-like symptoms. You may have a long history of inflammatory or rheumatoid arthritis and fibromyalgia.
Discussion points of this article:
- CRPS-I is more mysterious as it occurs without obvious or confirmed nerve injury.
- Types of complex regional pain syndrome.
- From injury or post-surgical complication to CRPS. The long journey seeking help.
- The patient’s poor understanding of CRPS was associated with greater disability and fear of movement.
- Complex regional pain syndrome is a complex and often poorly understood condition.
- Patients with Complex Regional Pain Syndrome will face significant quality of life consequences.
- The migraine headache – “CRPS of the brain” – is this a diagnostic tool?
- Migraine and complex regional pain syndrome.
- Circulatory problems and constricted blood vessels and exaggerated neurogenic inflammation.
- The autonomic nervous system response.
- Why do you have vision problems?
- The role of Anti-Inflammatory medications.
- Anticonvulsants and antidepressants for Complex Regional Pain Syndrome.
- Electrical Stimulation for Complex Regional Pain Syndrome.
- Addressing immobilization and ligament structural damage. Is this an “unknown” cause of Complex Regional Pain Syndrome?
- Following the path of CRPS through ligament damage.
- The nerve endings in ligaments and their impact in Complex Regional Pain Syndrome.
- Botulinum toxin and nerve blocks for Complex Regional Pain Syndrome type 1.
- Vitamin C and preventing Complex Regional Pain Syndrome type 1 after surgery.
- Prolotherapy treatments for Complex Regional Pain Syndrome.
- Treating migraines that have been unresponsive to other treatments by treating cervical spine instability. Could this be an answer?
- Migraine treatments that do not work, do not work because they do not address the problems of cervical spine instability from cervical ligament damage.
- Occipital allodynia (a super sensitivity to pain)
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.
In a June 2021 paper in the journal Pain and Therapy (1) doctors write of the current treatment plans:
“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.
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 in 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.
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. For some of these people, they do not truly understand what their type means. I also point out that many people that contact us do not even discuss a “Type.”
- Type I is the acute phase. In the acute phase, pain is described as burning or aching and is often aggravated by touch, emotional upset, or active/passive movement.
- Type II is the dystrophic phase, pain is constant. The pain is exacerbated by simple movement or sensation, such as touching, vibrating, or even blowing on the limb. The affected limb becomes even more edematous (swollen, fluid-filled) as well as cool and hyperhidrosis (sweaty).
- Type III is the atrophic stage. In the atrophic stage, irreversible damage to the extremity has occurred. The limb contracts (atrophy) because of limited movement. Skin becomes cool, thin, and shiny. Scar tissue has formed in soft tissue and because of this, it is difficult to move the joint at all. Osteoporosis and arthritis run rampant throughout the joint. This leads to a permanently frozen limb. The burning pain subsides, however at this stage, the limb is essentially useless. This process occurs over and over again in the body’s extremities.
From injury or post-surgical complication to CRPS. The long journey 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, 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 a meniscus and arthroscopic surgery. Three months later my knee is very painful, limited mobility, 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 maybe 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
The various diagnostic terms referring to CRPS
- Algodystrophy is a diagnostic term also known as complex regional pain syndrome.
- Causalgia describes the burning pain in a limb caused by nerve injury.
- Minor Causalgia describes the burning pain in a limb caused by nerve injury but the symptoms are not long-term in some and the situation is “minor” compared to Causalgia
- Chronic traumatic edema describes chronic swelling and increased skin temperature at the site of pain.
- Post-traumatic edema describes swelling and change in skin temperature following injury or reaction to surgery.
- Peripheral tropheneurosis describes changes in the skin including coloration, rash, lesions.
- Post-traumatic pain syndrome is also known as complex regional pain syndrome.
- Post-traumatic pain arthrosis (degenerative joint disease following injury or consequence of surgery).
- Shoulder-Hand syndrome describes pain and limited mobility in the shoulder with symptoms of swelling, skin color changes, and pain in the hands and fingers.
- Sudeck’s atrophy, Sudeck’s syndrome, and Sudeck’s dystrophy. These diagnoses are named for Paul Sudeck, MD a surgeon who in 1900 made a connection between pain, atrophy, skin discoloration and abnormalities including temperature and sweating, and motion difficulties with problems of the sympathetic nervous system.
- Sympathalgia is described in the medical literature as (2) lowering of the pain threshold (dysesthesia), vasomotor disturbance (dyskinesia or abnormality of voluntary movement, instability, clumsiness, tremors, seizures), local homeostatic disorders (dyscrasia – blood disorders), in certain circumstances trophic disturbances (dystrophy) which are usually accompanied by marked depression (dysthymia).
Complex regional pain syndrome is a complex and often poorly understood condition
An October 2020 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, 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), 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:
- 53 patients with CRPS (type 1 and type 2) completed questionnaires assessing illness perceptions, pain, disability, and psychological factors. Multiple factors were used to determine whether illness perceptions were associated with pain intensity, disability, depression, and kinesiophobia, (fear of movement).
- Negative illness perceptions were associated with greater pain, disability, and kinesiophobia, but not depression. Specifically, attributing more symptoms to CRPS (more negative illness identity perceptions) was associated with greater pain intensity, and reporting a poorer understanding of CRPS was associated with greater disability and kinesiophobia.
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 believing something can be done to help based on your own understanding of what Complex Regional Pain Syndrome is.
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 (4) 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.
Complex Regional Pain Syndrome no worse off than chronic musckuloskeletal pain
A March 2022 study comes to us from researchers in Germany. The findings were published in the European journal of pain (x) In this study the researchers compared epidemiological (the events that lead to the development of) pain and lifestyle factors of 223 CPRS patients from those of 255 people with chronic musculoskeletal pain without CPRS. One of the factors that the researchers noticed was that “in social media and the internet, high pain severity and the unfavorable prognosis are often empathized.” That in searching for information, most of the information people found was negative influencing.
Here are the findings:
- Patients with chronic musculoskeletal pain were more obese, drank more alcohol, and were less educated.
- Both groups smoked more than healthy people
- CRPS patients did not have more severe pain and did not suffer more from pain-related disability than patients with chronic musculoskeletal pain.
- Conclusion: In summary, our study supports a more optimistic view on pain in CRPS patients in comparison to MSK and identifies lifestyle factors that might contribute to the pathophysiology like smoking and drinking. Important next steps are the identification of CRPS patients at risk for chronification or-vice versa-with protective factors for pain resolution.
Significance: This study compares complex regional pain syndrome (CRPS) and chronic musculoskeletal pain and questions previously reported pain, disability and lifestyle factors associated with CRPS.
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 multicentre trial: low-dose intravenous immunoglobulin treatment for long-standing Complex Regional Pain Syndrome (LIPS trial).”(5)
- Continuing pain, which is disproportionate to any inciting event. (you have more pain than the initial injury should be causing).
- Must report at least one symptom in all four of the following categories:
- sensory – reports of hyperaesthesia excessive pain sensitivity, especially of the skin, and/or allodynia.
- Must report at least one symptom in all four of the following categories:
Let’s pause here for an explanatory note:
We often see patients with very heightened sensitivity to pain, especially the skin. A cool breeze will “burn,” an 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 (6) 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: Patient must display at least one sign at time of evaluation in two or more of the following categories:
- vasomotor – reports of temperature asymmetry and/or skin color changes and/or skin color asymmetry.
- sudomotor/edema – reports of edema and/or sweating changes and/or sweating asymmetry.
- motor/trophic – reports of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin).
Must display at least one sign at time of evaluation in two or more of the following categories:
- Sensory – evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch and/or temperature sensation and/or deep somatic pressure and/or joint movement).
- Vasomotor – evidence of temperature asymmetry and/or skin color changes and/or asymmetry
- Edema – evidence of edema and/or sweating changes and/or sweating asymmetry
- Motor/trophic – evidence of a decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)
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 (7) made these observations in connecting migraine headaches and 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%)
- Higher migraine frequency was associated with a longer CRPS duration.
- Migraine headaches sufferers who developed CRPS had a higher prevalence of psychological and medical disorders.
- Alleviating migraine’s psychological and medical comorbidities may help lower CRPS occurrence.
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 in helping patients with simple dextrose injections into painful areas. The highlights and learning points of this paper are present 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 (8) 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 (9)
Circulatory problems and constricted blood vessels and exaggerated neurogenic inflammation
- Complex Regional Pain Syndromes (CRPS) are characterized by vascular disturbances (circulatory problems) primarily affecting the microcirculation in the distal (furthest) part of the involved extremity. In the acute stage inhibited sympathetic vasoconstriction (Vasoconstriction reduces circulation by contracting the space within blood vessels while increasing blood pressure) and exaggerated neurogenic (nerve) inflammation driven by central and peripheral mechanisms, respectively, seem to be the major pathophysiological mechanisms inducing vasodilation.”
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:
- Burning, tingling, constant “pins and needles,” or “electric” sensations
- Severe or painful muscle spasms or cramps
- “Numbness” (a transient sensation of numbness that comes and goes with certain movements) or numbness (true chronic numbness caused by nerve impingement.)
- Muscle fatigue or muscle weakness
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 sensation 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.
- Peripheral nervous system dysfunction can impact:
- The Somatic nervous system is the voluntary muscular control of body movements. (You see a tool and pick it up. That is a voluntary muscular control movement). Here you may have symptoms of muscle weakness or inability to perform simple tasks.
- Cervical spinal nerves (C1–C4). These nerves control head and neck movements, sensations in the head. The C4 impacts the upper shoulder. These can be areas of pain sensations in CRPS.
- Brachial plexus. Plexus is a network of interconnecting nerves (C5–T1). In problems of CRPS, the Brachial plexus can cause heightened pain by impacting the muscles of the chest, shoulders, arms, and hands.
- The lumbosacral plexus provides the nerve sensation in the lumbar/low back, buttocks, groin, thighs, male and female genitalia (nerve bundles frequently injured in childbirth), knees, and calves.
Why do you 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 (10), 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 for 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.
The role of Anti-Inflammatory medications
A June 2020 study in the journal Pain and Therapy (11) 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 which 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 the 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.
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 your involuntary muscle movement.
A 2014 study (12) 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.
Anticonvulsants and antidepressants for Complex Regional Pain Syndrome
November 2020 research from the University of Texas published in the journal Pain Management (13) 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 whether these drugs are effective in reducing CRPS-related pain. . . Overall, evidence (published research) is considered insufficient for 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 (14) 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:
- 16 patients (10 women and 6 men, age 26-61 years) suffering from Complex Regional Pain Syndrome Type 1 related foot and leg pain.
- All 16 patients had failed conventional medical management.
- Seven subjects were previously treated with Spinal Cord Stimulator (SCS) Systems for CRPS I pain. These subjects reported pain relief in the thigh and leg, however, the SCS was unable to alleviate the disabling foot pain despite varied and multiple programming techniques.
- The remaining nine subjects were treated primarily with Direct Sciatic Nerve Electrical Stimulation.
- This study shows that Direct Sciatic Nerve Electrical Stimulation helps to control the disabling foot pain in CRPS I, thus improving the quality of life, improving ambulation, and decreasing disability.
Addressing immobilization and ligament structural damage. Is this an “unknown” cause of Complex Regional Pain Syndrome?
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 into 2020.
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 do not heal. Stress deprivation or immobility causes a protracted state of progressive atrophy and a lack of mechanical strength in the injured ligaments.
- Most cases of CRPS occur after some type of trauma to bones, joints, and soft tissues. One of the tissues injured in these traumas is ligaments. A ligament connects two bones and is involved in the stability of the joint. A sprain is a stretched or injured ligament. Because ligaments generally have a poor blood supply, incomplete healing is common after injury.
Prolonged immobilization, loss of motion
- Motion loss of the joint, connected by the ligament, is also common after injury. This is increased when multiple ligaments are injured, the joint is dislocated, or if surgery or prolonged immobility occurs after the ligament injury.
- Prolonged immobilization has detrimental effects on periarticular cartilage, bone, and soft tissues and can lead to more motion loss.
- During immobilization, connective tissues shorten (or atrophy), thereby further decreasing the range of motion of the joint. Please see our article: Ligament and tendon damage from Immobilization syndrome, In this article, we review various aspects of short and long-term immobilization of an injured joint, specifically the damage to the tendons and cartilage. Immobilization syndrome has been implicated in being a developmental cause of long-term chronic joint pain and possibly CRPS.
- The negative effects of periodic short-term immobilization on joints and soft tissues are cumulative.
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.
A case reported in the medical literature, immobilization of the ankle leads to CRPS
A 2019 paper (15) in the Journal of Orthopedic Case Reports presented a case at King Edward Memorial Hospital. Here are the learning points:
- A 30-year-old female presented 2 months after trauma to the right ankle due to a fall from a bike.
- A radiograph of the ankle demonstrated no evidence of any bony injury. As per records, there was no evidence of ligament injury based on magnetic resonance imaging evaluation.
- As the patient had severe pain and swelling, she underwent conservative treatment in the form of lower limb immobilization in a non-weight-bearing below-knee flexible cast for a period of 8 weeks.
- After removal of the cast, the patient continued to have severe pain and swelling and was unable to bear weight. At this point in time, the patient presented to our clinic where follow-up radiographs demonstrated a bimalleolar fracture of the right ankle and diffuse osteoporosis involving talus-calcaneus and metatarsals.
- The diagnosis of CRPS was made
- This case report highlights the importance of the multimodal stepped care approach in CRPS 1 involving the ankle joint. Our report also reiterates the relevance of early mobilization and avoiding undue immobilization.
Botulinum toxin and nerve blocks for Complex Regional Pain Syndrome type 1
A December 2021 study in Anesthesiology (16) tested the hypothesis that botulinum toxin would prolong the duration of a lumbar sympathetic block measured through a sustained increase in skin temperature. A total of 48 patients, 24 would get the botulinum toxin and 24 would get the placebo 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.
Vitamin C and preventing Complex Regional Pain Syndrome type 1 after surgery
A November 2021 study in The Journal of Foot and Ankle Surgery (17) examined complex regional pain syndrome type 1 (CRPS-I) complications after limb extremity surgeries and if vitamin C in 500 mg dosage helped. The researchers wrote that controversy exists regarding the effectiveness of vitamin C in reducing the possibilities of the development of Complex regional pain syndrome type 1 following limb surgeries. These researchers then conducted a systematic review and meta-analysis to assess the role of vitamin C on CRPS-I and functional outcomes after distal radius, wrist, foot, and ankle surgeries. The timeframe for vitamin C administration ranged from 42 to 50 days post-injury and/or surgical fixation. The effect size showed that vitamin C was associated with a decreased rate of CRPS-1 than placebo. No significant difference was found between vitamin C and placebo in terms of complications, functional outcomes, and pain scores. These results hold true when stratifying fracture type (distal radius, ankle, and foot surgeries) and vitamin C dose (500 mg or 1 g).
Prolotherapy treatments for Complex Regional Pain Syndrome
Prolotherapy is considered an alternative treatment for:
- commonly prescribed anti-inflammatory medications
- pain medications
- cortisone or steroid injection
- surgery and joint replacement
The basic concept of Prolotherapy is simple. A proliferant (something that awakens and ignites the immune system’s healing process) is injected into damaged joint 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 to 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 (18) 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. (19) Here researchers wrote:
- “Understanding of the precise mechanisms of the relationship between Cervical Spondylosis and migraine risk remains limited. Cervical vertebral degenerative processes can compromise the capsular ligaments of facet joints, thereby contributing to the hypermobility of upper cervical vertebrae. Such cervical instability causes the dysregulation of the vertebrobasilar arteries, which leads to migraines.”
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 (20) 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.
- Occipital allodynia (a super sensitivity to pain) is common, as is a spasm of the cervical muscles. Patients with Unremitting head and neck pain may comprise a subgroup of Chronic Migraines, as well as Chronic Tension-Type Headache, New Daily Persistent Headache, and Cervicogenic Headache.
- Centrally acting membrane-stabilizing agents (local anesthetics), which are often ineffective for Chronic Migraines, are similarly generally ineffective for unremitting head and neck pain.”
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.
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 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
Brian Hutcheson, DC | Ross Hauser, MD | Danielle Steilen-Matias, PA-C
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This article was updated July 1, 2021