Complex Regional Pain Syndrome (CRPS)

Complex regional pain syndrome (CRPS) is a long-lasting pain problem that usually starts in one arm, hand, leg, or foot after an injury or a medical event. The pain is much stronger than expected for that injury, and it lasts longer than normal healing time. CRPS also affects skin, blood flow, sweat, movement, and the way nerves send danger signals. It is not “just in the mind.” It is a real body condition that can change how the nervous system and the immune system act in that body part. [NINDS]

Complex regional pain syndrome (CRPS) is a long-lasting pain condition that usually starts after an injury, surgery, or even a small trauma to an arm or leg. The pain is much stronger and lasts much longer than you would normally expect from the original injury. People often feel burning pain, swelling, color and temperature changes in the skin, sweating changes, and stiffness in the joints of the affected limb.[1] Scientists think CRPS happens because the nervous system, immune system, and blood vessels in that area become over-active and “stuck” in a pain and inflammation loop.[2][3] Early diagnosis and a mix of physical, psychological, and medical treatments give the best chance of recovery.[4]

CRPS is called “regional” because it usually involves a region (like a hand and wrist), not only one tiny spot. It is called a “syndrome” because it is a group of signs and symptoms (pain + swelling + color/temperature changes + sensitivity + movement problems). There is no single test that proves CRPS by itself. Doctors mainly diagnose it by careful history and exam, using a clear rule set (the Budapest criteria). [Faculty of Pain Medicine]

Many experts describe CRPS as a problem where the body’s alarm system stays “on.” Nerves can become too sensitive (so normal touch feels painful), and small blood vessels and sweat glands can behave in a strange way (so the skin becomes hot/cold, red/blue, or too sweaty/dry). Muscles and joints can become stiff because the person avoids moving due to pain, and because the nervous system can change motor control. [Mayo Clinic]

Other names

CRPS has been known by older names. CRPS Type I was often called Reflex Sympathetic Dystrophy (RSD). CRPS Type II was often called Causalgia (usually when there is a clear nerve injury). Today, “CRPS” is the main name used in modern medical sources. [NINDS]

Types

• CRPS Type I (no confirmed major nerve injury): Symptoms fit CRPS, but tests and history do not show a clear major nerve cut or major nerve damage. This is the more common type. [NINDS]

• CRPS Type II (with confirmed major nerve injury): Symptoms fit CRPS and there is evidence of a clear nerve injury (for example after trauma or surgery). It was historically linked with “causalgia.” [PMC review]

Some doctors also describe “warm” (more red/hot/swollen early) and “cold” (more pale/blue/cool later) patterns, but the official main split is Type I vs Type II. [Stanford Medicine]

Causes (what can start CRPS)

1. Bone fracture: A broken bone (especially wrist or ankle) can trigger CRPS during or after healing. [NINDS]

2. Sprain or strain: Even a “small” injury can start CRPS in some people. The pain becomes larger than expected. [NINDS]

3. Surgery: CRPS can begin after an operation, even when the surgery was done correctly. [Mayo Clinic]

4. Nerve injury (major nerve damage): This is a classic trigger for CRPS Type II. [PMC review]

5. Minor nerve irritation: Sometimes nerves are not “cut,” but they can be irritated or stretched, and CRPS-like changes can start. [NINDS]

6. Cast or tight bandage problems: Pressure, swelling, and reduced movement after immobilization may contribute in some cases. [Mayo Clinic]

7. Soft tissue injury: Injury to skin, muscle, or ligaments can trigger a pain response that does not turn off normally. [NINDS]

8. Work or sports trauma: Repeated injuries or one strong hit may be a start point in some patients. [Cleveland Clinic]

9. Heart attack (myocardial infarction): A medical event like a heart attack has been reported as a trigger in some people. [NINDS]

10. Stroke: After a stroke, some people develop CRPS-like pain and swelling in one limb. [NINDS]

11. Spinal cord problems: Some nervous system injuries can change pain control and may be linked with CRPS in certain cases. [NINDS]

12. Inflammation that stays high: The immune system can stay active too long after injury, adding swelling and sensitivity. [NINDS]

13. Abnormal sympathetic nerve activity: The “fight or flight” nerve system may overreact, affecting blood flow and sweat. [Mayo Clinic]

14. Poor nerve “reset” after healing: The nervous system may keep sending danger signals even after tissues heal. [NINDS]

15. Severe pain early after injury: Strong early pain and fear of movement can lead to guarding and stiffness, which may worsen the cycle. [Cleveland Clinic]

16. Infection after injury or surgery: Infection can increase inflammation and nerve sensitivity, and in rare cases may be part of the story. [Mayo Clinic]

17. Poor circulation response: Some people have stronger blood vessel reactions (hot/cold changes), which may support CRPS changes. [Mayo Clinic]

18. Autoimmune-like reactions (possible factor): Some research discusses immune antibodies and inflammation as possible contributors, but this is not always proven for each person. [Review]

19. No clear trigger (idiopathic): In some patients, CRPS starts without a known injury. This can happen, even though it is less common. [Cleveland Clinic]

20. Combination triggers: Often it is not one cause. It may be injury + immobilization + strong inflammation + nerve sensitization together. [NINDS]

Symptoms (what a person may feel or notice)

1. Severe ongoing pain: Pain can feel burning, throbbing, stabbing, or deep aching, and it lasts longer than expected. [Mayo Clinic]

2. Pain from light touch (allodynia): A light brush of clothing can hurt a lot. [Review]

3. Extra pain from pinprick or pressure (hyperalgesia): A small painful thing feels much more painful than normal. [Review]

4. Swelling: The limb may swell and feel tight. Swelling can come and go. [Mayo Clinic]

5. Skin temperature change: The skin may become warmer or cooler than the other side. [Mayo Clinic]

6. Skin color change: Skin may look red, purple/blue, pale, or blotchy. [Mayo Clinic]

7. Sweating change: The area may sweat too much or too little compared to the other side. [Mayo Clinic]

8. Skin texture change: Skin can become shiny, thin, or very sensitive. [Mayo Clinic]

9. Hair and nail changes: Hair or nails may grow faster or slower, or look different. [Mayo Clinic]

10. Stiff joints and reduced movement: Moving the hand/foot may become hard due to pain and stiffness. [Mayo Clinic]

11. Muscle weakness: The limb may feel weak because pain blocks normal use and muscles can shrink over time. [Mayo Clinic]

12. Tremor or muscle spasms: Shaking or spasms can happen in some people. [Mayo Clinic]

13. Sensitive to cold: Cold air or cool water may cause strong pain. [Mayo Clinic]

14. Changes in limb shape or “trophic” changes: Long-term CRPS can change soft tissue and bone, and the limb can look different. [Stanford Medicine]

15. Symptoms spreading: Sometimes symptoms move beyond the first area, but this does not happen to everyone. [NINDS]

Diagnostic tests

(Important: CRPS is mainly a clinical diagnosis. Tests are often used to support the diagnosis or to rule out other problems.) [Mayo Clinic]

Physical exam tests (doctor looks, feels, compares)

1. Budapest clinical criteria check: The doctor confirms (a) ongoing pain out of proportion, (b) symptoms in categories, and (c) signs on exam in categories, and (d) no better diagnosis explains it. This is the main diagnostic method. [Faculty of Pain Medicine]

2. Temperature comparison: The doctor compares skin temperature of both limbs (for example with the back of the hand or a thermometer). Big differences support vasomotor change. [Mayo Clinic]

3. Color and swelling check: The doctor looks for redness, mottling, bluish color, and swelling compared with the other side. [Mayo Clinic]

4. Range of motion exam: The doctor checks how far joints move and how pain limits movement. Stiffness is common in CRPS. [Mayo Clinic]

5. Strength and muscle size exam: The doctor checks weakness and any muscle wasting from reduced use. [Mayo Clinic]

Manual tests (hands-on pain and nerve sensitivity tests)

6. Light touch test (cotton/brush): The clinician lightly touches the skin to see if it causes pain (allodynia). [Review]

7. Pinprick test: A gentle pinprick checks if sharp sensation feels too painful (hyperalgesia). [Review]

8. Vibration test (tuning fork): Vibration can feel unpleasant or painful in sensitized nerves. It helps map sensory change. [Review]

9. Two-point discrimination: The doctor checks if the brain has trouble telling two close points apart on the skin, which can change in chronic pain states. [Review]

Lab and pathological tests (blood/urine tests to rule out other causes)

10. Inflammation markers (ESR/CRP): These can help rule out strong infection or inflammatory arthritis if swelling is present. They do not prove CRPS but help exclude other diseases. [Review]

11. Complete blood count (CBC): Helps rule out infection or blood disorders when symptoms look unusual. Not a CRPS proof test. [Review]

12. Autoimmune screening (when needed): Tests like ANA or rheumatoid-related tests may be used if the doctor suspects autoimmune joint disease instead of CRPS. [Review]

13. Metabolic tests (thyroid, glucose, B12 when needed): These help rule out nerve pain from diabetes, thyroid problems, or vitamin deficiency. They support “not another cause.” [Review]

Electrodiagnostic tests (nerve and muscle signal tests)

14. Nerve conduction studies (NCS): Measures how fast and how well nerves carry signals. This can help find a true nerve injury (important for Type II) or other neuropathy. [PMC review]

15. Electromyography (EMG): Checks muscle electrical activity to look for nerve damage patterns or other neuromuscular disease. It helps rule out other causes of weakness. [PMC review]

Imaging and specialized tests (supportive tests)

16. Three-phase bone scan: Can show bone metabolism changes that may appear in CRPS, especially earlier in some cases. It supports, but does not confirm alone. [Mayo Clinic]

17. X-ray of the limb: In later stages, bone thinning (loss of minerals) may be seen. Normal X-ray does not rule out CRPS. [Mayo Clinic]

18. MRI: Can help rule out other problems (like tissue injury, joint disease, infection, or nerve compression) and may show swelling or tissue changes. [Review]

19. Thermography (temperature imaging): Measures heat patterns and side-to-side differences. It can support vasomotor change, but it is not a single “proof.” [Review]

20. Sweat production tests (QSART or similar): Tests whether sweating differs between limbs. Uneven sweating supports sudomotor changes seen in CRPS. [Mayo Clinic]

Non-pharmacological treatments

Non-drug treatments are the foundation of CRPS care. The main goals are to reduce pain, keep the limb moving, prevent stiffness, and calm the nervous system. These approaches are usually used together in a personalized program led by a pain team, physiotherapist, and psychologist.[5]

1. Patient education and self-management
Education means giving clear, simple information about what CRPS is, why pain is strong, and how movement and treatment help the brain “reset” its pain signals.[6] When people understand that pain does not always mean new damage, they are less scared to move. This reduces fear, stress, and “guarding” of the limb. Good education also teaches pacing (doing activities in small, regular steps) and goal-setting. Over time this can lower pain, improve function, and increase confidence.[7]

2. Early mobilization and graded physical therapy
Gentle, guided movement of the affected limb is one of the most important treatments. A physiotherapist usually starts with very small, pain-limited movements and slowly increases the time and range as tolerated.[8] This helps prevent joint stiffness, muscle wasting, and bone loss. Regular movement also sends more “normal” signals to the brain, which can reduce over-sensitivity. The key idea is “little and often,” not pushing into severe pain.

3. Graded motor imagery (GMI)
Graded motor imagery is a step-by-step brain training program. It usually starts with left–right hand or foot recognition, then imagined movements, and finally mirror therapy.[9] The person does not move the painful limb at first. Instead, they train the brain to think about movement in a safe way. Studies show GMI can clearly reduce pain and improve function in long-standing CRPS by changing how the brain processes pain signals.[10][11]

4. Mirror therapy
In mirror therapy, the unaffected limb is placed in front of a mirror, and the painful limb is hidden behind it. When the person moves the healthy limb, the mirror makes it look like the painful one is moving normally.[12] This tricks the brain into seeing pain-free movement and helps “re-map” the painful area. Mirror therapy can reduce pain and improve motor function, especially in early or post-stroke CRPS.[13]

5. Desensitization therapy
Desensitization means slowly exposing the skin to different gentle textures, temperatures, and pressures, such as cotton, silk, sponge, or cool/warm cloths.[14] Sessions start very short and are increased gradually. The goal is to teach the nerves and brain that light touch is safe again, so they stop sending strong pain signals. Over time, this can reduce allodynia (pain from light touch) and make daily tasks more tolerable.[15]

6. Occupational therapy and functional training
Occupational therapists focus on everyday tasks like dressing, cooking, writing, keyboard use, and personal care. They break activities into small steps, teach pacing, and may give splints or adaptive tools to protect joints while still using the limb.[16] The aim is to keep the person independent and engaged in life, which also reduces depression and anxiety linked with chronic pain.[17]

7. Constraint-induced movement therapy
In some people, the healthy limb is gently limited (for example, with a removable mitt) for short, supervised times, so the person is encouraged to use the painful limb more.[18] This must be done carefully by a specialist team and only when it is safe. Research suggests it can improve function by forcing the brain to re-use the affected side, but it should not be used in very severe or early swollen CRPS.[19]

8. Aquatic (water-based) therapy
Moving the limb in warm water can be more comfortable because water supports the weight of the limb and warmth relaxes muscles.[20] Exercises like gentle walking, arm swings, or knee bends in a pool can improve range of motion and blood flow and reduce fear of movement.[21] Warm water also soothes the autonomic nervous system, which may help with color and temperature changes in CRPS.

9. TENS (transcutaneous electrical nerve stimulation)
TENS uses small electrical pulses through skin pads to “distract” the nervous system from pain. The stimulation is usually mild and non-painful. By activating non-painful nerve fibers, TENS can reduce the transmission of pain signals to the spinal cord and brain.[22] Some people with CRPS report short-term pain relief that allows them to move more easily, although research results are mixed.

10. Functional restoration programs
These are intensive, team-based programs that combine physical therapy, occupational therapy, psychological support, and pain education over several weeks.[23] The focus is not only on pain scores but also on returning to daily roles, school, or work. Stepwise increases in activity are planned and monitored. Studies suggest that such programs can improve function and quality of life, even when pain does not disappear completely.[24]

11. Cognitive behavioral therapy (CBT)
CBT is a psychological therapy that helps people notice and change unhelpful thoughts (“my leg is ruined forever”) and behaviors (avoiding all movement).[25] In CRPS, CBT aims to reduce fear of pain, depression, and anxiety, and to improve coping and sleep. By lowering stress hormones and muscle tension, CBT can indirectly reduce pain intensity and disability.[26]

12. Mindfulness and relaxation training
Mindfulness meditation, breathing exercises, and progressive muscle relaxation teach the body to shift from “fight or flight” into a calmer state.[27] Regular practice can lower heart rate, improve sleep, and reduce the emotional “alarm” linked with chronic pain. Studies in chronic pain show small to moderate improvements in pain and quality of life with mindfulness-based stress reduction programs.[28]

13. Biofeedback
In biofeedback, sensors measure things like muscle tension, skin temperature, or heart rate and show them on a screen. The person learns how breathing, relaxing muscles, or changing posture can change these signals.[29] Over time, biofeedback can help people gain better control over bodily stress responses, which may ease pain and improve circulation in the affected limb.[30]

14. Sleep hygiene strategies
Chronic pain and poor sleep feed each other. Simple sleep rules include keeping a regular bedtime, limiting screens before bed, avoiding heavy meals and caffeine late in the day, and making the bedroom quiet and dark.[31] Better sleep can reduce pain sensitivity, irritability, and fatigue, making it easier to engage in physical and psychological therapies for CRPS.[32]

15. Graded exposure to activity and fear-avoidance training
Some people with CRPS fear that any movement will “damage” the limb more. Graded exposure means slowly facing feared activities (like brushing the skin or putting weight through the foot) in a controlled way.[33] The therapist helps the person notice that nothing bad happens, so fear and pain intensity can drop over time. This approach is part of modern pain rehabilitation and is supported by studies in various chronic pain disorders.[34]

16. Vocational and school rehabilitation
For adults, work-focused rehab, and for young people, school-based support, help them return to meaningful roles. Plans may include modified duties, part-time schedules, or ergonomic changes.[35] Staying engaged with work or school reduces isolation, financial stress, and low mood, which all can worsen pain.

17. Temperature and contrast therapy (used cautiously)
In some people, carefully controlled warm or contrast (warm–cool) baths of the limb may help improve circulation and reduce swelling.[36] Water should never be very hot or very cold, as extreme temperatures can trigger flares. This method is usually guided by a therapist and avoided in very sensitive or early inflammatory stages.

18. Compression garments and gentle elevation
Soft compression gloves, stockings, or wraps can help manage swelling and support joints.[37] Combined with regular elevation of the limb above heart level, this can reduce edema and heaviness. Care is needed to avoid tight garments or bandages that might worsen pain or cut off blood flow.

19. Support groups and peer programs
Meeting others with CRPS—either in person or online—can reduce feelings of being alone and misunderstood. People share coping strategies, ask questions, and feel more hopeful when they see others improving.[38] Peer support is not a cure, but it helps mental health and adherence to treatment plans.

20. Complementary therapies (e.g., acupuncture, massage, yoga)
Some people find additional benefit from acupuncture, gentle massage away from the most sensitive area, or adapted yoga and stretching.[39] Evidence in CRPS is limited and mixed, but these may help relaxation, mood, and general fitness when used alongside standard treatments. They should be done by trained professionals who understand CRPS and avoid aggressive techniques.

---

Drug treatments

Drug treatments are usually added when non-drug therapies are not enough. Many medicines used in CRPS are off-label, meaning they are approved by the FDA for other pain or mood conditions but are used for CRPS based on studies and expert opinion.[40] Doses here are typical adult ranges from FDA labels or pain guidelines and must always be adjusted by a doctor.

1. Non-steroidal anti-inflammatory drugs (NSAIDs – ibuprofen, naproxen)
NSAIDs are pain-relief and anti-inflammatory medicines that block cyclo-oxygenase (COX) enzymes and lower prostaglandins, which drive inflammation.[41] Typical adult doses include ibuprofen 400–800 mg every 6–8 hours or naproxen 250–500 mg twice daily, with meal and stomach protection as needed. They may help early CRPS after an injury but are usually not enough alone in long-standing disease. Side effects include stomach ulcers, kidney strain, and increased blood pressure.

2. Acetaminophen (paracetamol)
Acetaminophen reduces pain and fever by acting in the brain on COX enzymes and other pathways.[42] A common adult limit is up to 3,000–4,000 mg per day (for example, 500–1,000 mg every 6 hours), but doctors often recommend lower limits in people with liver or alcohol problems. It is often combined with other treatments for background pain relief. Too high a dose can severely damage the liver, so the daily maximum must never be exceeded.

3. Oral corticosteroids (e.g., prednisone)
Short courses of steroids may be used early in CRPS to calm strong inflammation, swelling, and redness.[43] Prednisone doses can start around 30–60 mg daily and are slowly reduced over several weeks under specialist supervision. Steroids act by blocking many inflammatory genes and immune cells. They can improve mobility and pain in some early cases, but long-term use risks weight gain, diabetes, bone weakening, mood changes, and infection.

4. Gabapentin (Neurontin)
Gabapentin is a gabapentinoid used for nerve pain. It binds to alpha-2-delta subunits of voltage-gated calcium channels in the nervous system, reducing abnormal nerve firing.[44] FDA labels support doses up to 1,800–3,600 mg per day in divided doses for neuropathic pain conditions.[45] Trials in CRPS suggest modest pain relief in some patients.[46] Common side effects are dizziness, sleepiness, weight gain, and swelling in the legs.

5. Pregabalin (Lyrica)
Pregabalin is similar to gabapentin but has more predictable absorption. It also targets alpha-2-delta calcium channel subunits to lower nerve excitability.[47] FDA-approved doses for neuropathic pain are often 150–600 mg per day in two or three doses.[48] Case series and guidelines report its use in CRPS with reductions in burning pain and sleep disturbance for some patients. Side effects include dizziness, drowsiness, weight gain, swelling, and sometimes blurred vision.

6. Tricyclic antidepressants (e.g., amitriptyline)
These older antidepressants block the re-uptake of serotonin and noradrenaline in the spinal cord, which strengthens the body’s own pain–inhibiting pathways.[49] Low doses (10–75 mg at night) are used for nerve pain and sleep, not mainly for depression. They may reduce CRPS pain and improve sleep quality. Side effects can include dry mouth, constipation, weight gain, low blood pressure, and heart rhythm changes, so monitoring is needed.

7. SNRIs – duloxetine (Cymbalta)
Duloxetine is a serotonin–noradrenaline re-uptake inhibitor used for depression, anxiety, and several chronic pain conditions.[50] FDA labels support 30–60 mg once daily for neuropathic and musculoskeletal pain.[51] In CRPS, it may help nerve pain, mood, and sleep at the same time. Side effects include nausea, dry mouth, sweating, raised blood pressure, and, rarely, liver issues. Some duloxetine lots have been recalled due to nitrosamine impurities, which doctors monitor carefully.[52]

8. Topical lidocaine 5% patch (Lidoderm)
Lidocaine patches are placed on intact skin over the painful area for up to 12 hours per day.[53] Lidocaine blocks sodium channels in nerve endings, stopping pain signals before they reach the spinal cord. In CRPS, they may reduce localized allodynia and burning pain, especially in small, well-defined areas. Side effects are usually mild skin irritation or numbness, but large or prolonged use can rarely cause systemic toxicity.

9. Topical capsaicin (cream or high-strength patch)
Capsaicin, from chili peppers, activates TRPV1 receptors on pain nerves. With repeated application, these receptors become less sensitive and pain signals drop.[54] Lower-strength creams are applied several times a day, while high-strength patches are used in clinic. In localized CRPS pain, capsaicin may reduce burning and touch sensitivity. Side effects include burning or stinging at the site, especially in early use.

10. Bisphosphonates – alendronate (Fosamax)
Alendronate is a bisphosphonate that strongly binds to bone and blocks osteoclast-mediated bone breakdown.[55] Studies in CRPS show that both oral and intravenous bisphosphonates can reduce pain and improve bone changes, likely by calming bone inflammation.[56] Typical osteoporosis doses are 70 mg once weekly or 10 mg daily, taken on an empty stomach with water while sitting upright.[57] Side effects include stomach upset, esophagus irritation, and rare jaw or thigh bone problems.

11. Other bisphosphonates – pamidronate, clodronate
Intravenous pamidronate or clodronate can be given in hospital infusions for severe CRPS with bone changes.[58] They also inhibit bone resorption and may reduce inflammatory substances in bone. Trials report meaningful pain relief and improved movement in some patients after short infusion courses. Side effects include flu-like symptoms after the first dose, low calcium, and kidney strain, so blood tests are required.

12. Calcitonin (Miacalcin)
Calcitonin-salmon nasal spray or injection is an older osteoporosis medicine that decreases bone resorption and may have direct pain-modulating effects.[59] It has been used off-label in CRPS, mainly in earlier stages, with mixed evidence. Typical nasal doses are 200 IU once daily, alternating nostrils.[60] Side effects include nasal irritation, flushing, and, in long-term high-dose studies, a possible small increase in some cancers, so guidelines now use it carefully.

13. Weak opioids – tramadol
Tramadol acts on opioid receptors and also weakly blocks serotonin and noradrenaline re-uptake. It can be used short-term for moderate CRPS pain not controlled by other drugs.[61] Adult doses may range up to 200–300 mg per day in divided doses, but doctors keep doses low and duration short. Side effects include nausea, dizziness, constipation, drowsiness, and, at higher doses, seizure risk.

14. Strong opioids (e.g., morphine, oxycodone – last resort)
In very severe, short-term situations, stronger opioids may be considered under strict specialist control, often while other treatments are started.[62] They act on mu-opioid receptors to strongly dampen pain signals. However, long-term opioids can lead to tolerance, dependence, hormonal changes, constipation, and even increased pain sensitivity. Modern guidelines recommend avoiding or minimizing long-term opioid use in CRPS.

15. Ketamine (IV or topical – off-label)
Ketamine blocks NMDA receptors, which are key in central sensitization, a major mechanism in CRPS.[63] Low-dose intravenous infusions given in hospital or compounded topical creams can reduce pain for some time in people with severe CRPS. Treatment is usually short blocks repeated if helpful. Side effects include vivid dreams, dizziness, blood pressure and heart-rate changes, and nausea, so close monitoring is essential.

16. Clonidine (oral or patch)
Clonidine stimulates alpha-2 receptors and reduces norepinephrine release, calming the sympathetic nervous system. Because CRPS often involves abnormal sympathetic activity (cold, sweaty, or color-changed limb), clonidine may help in selected cases.[64] It can be given as tablets or a patch. Side effects include low blood pressure, dry mouth, and sleepiness.

17. Baclofen (oral or intrathecal)
Baclofen is a GABA-B receptor agonist that reduces muscle spasticity and abnormal reflexes.[65] In CRPS with strong muscle spasms or dystonia, baclofen can be used by mouth, and in very severe cases, through a pump into the spinal fluid (intrathecal). Side effects include weakness, drowsiness, and dizziness. Stopping suddenly can cause severe withdrawal, so doses must be changed slowly.

18. Botulinum toxin injections
Botulinum toxin blocks acetylcholine release at the neuromuscular junction, relaxing muscles, and may also reduce pain mediators in the skin.[66] For CRPS with focal dystonia or severe local pain, injections into specific muscles or skin areas can reduce pain and improve position and function. Side effects are usually local weakness or bruising at the injection site.

19. NMDA-modulating oral agents (e.g., memantine – experimental)
Memantine is an NMDA receptor antagonist used for Alzheimer’s disease, but it has been explored in neuropathic pain.[67] In CRPS, small reports suggest possible benefit, but evidence is limited. Doses and monitoring follow dementia labels, and side effects include dizziness, confusion, and high blood pressure. It remains experimental for CRPS and is only used in research-minded specialist centers.

20. Anti-TNF biologics – infliximab, etanercept (highly specialized)
Because inflammatory cytokine TNF-α is high in CRPS-affected tissues, anti-TNF drugs like infliximab or etanercept have been tried.[68] Case series and small studies show pain and swelling improvements in some patients, but others do not respond, and there are risks like infection and allergic reactions.[69] These medicines are given by injection or infusion and are reserved for severe, refractory CRPS in research or specialized centers only.

---

Dietary molecular supplements

Dietary supplements may support general health, reduce inflammation, and sometimes lower pain, but they do not replace core physical and medical treatments. Doses must be checked with a doctor, especially if the person is young, pregnant, has kidney or liver problems, or takes other medicines.

1. Vitamin C (ascorbic acid)
Vitamin C is a strong antioxidant that protects tissues from free-radical damage and supports collagen and immune function. Several studies show that taking 500 mg of vitamin C daily for about 50 days after a wrist fracture reduces the chance of developing CRPS.[70] In people who already have CRPS, vitamin C may support tissue healing and immune health, although data are less clear. Too high doses can cause stomach upset and kidney stones in at-risk people.

2. Omega-3 fatty acids (EPA/DHA from fish oil)
Omega-3 fats from fish oil are converted into resolvins and protectins, which actively turn off inflammation and may reduce nerve pain.[71] Clinical and animal studies suggest omega-3s can improve symptoms in several neuropathic pain conditions.[72] Typical supplemental doses range from 1–3 g/day of combined EPA/DHA with food, under medical advice. Common side effects are fishy taste and mild stomach upset; higher doses can thin the blood.

3. Vitamin D
Vitamin D helps bone health, muscle function, and immune regulation. Low vitamin D is common in chronic pain and is linked to worse symptoms.[73] For deficiency, doctors may use 800–2,000 IU daily or higher short-term loading doses. In CRPS, correcting deficiency may support bone strength and possibly mood and pain, although specific CRPS trials are limited. Too much vitamin D can cause high calcium, kidney stones, or confusion, so blood tests are important.

4. Magnesium
Magnesium blocks NMDA receptors and helps nerve and muscle function. Intravenous magnesium has shown modest benefit in some neuropathic pain studies, and oral magnesium may support these effects.[74] Typical supplemental doses are around 200–400 mg elemental magnesium per day, depending on the form. Side effects include diarrhea and, at high doses in kidney disease, dangerous high magnesium levels, so medical advice is needed.

5. Alpha-lipoic acid (ALA)
ALA is an antioxidant that can regenerate other antioxidants like vitamin C and E. It has evidence in diabetic neuropathy for reducing burning and numbness.[75] Doses in studies are often 300–600 mg once or twice daily. In CRPS, ALA may help nerve metabolism and reduce oxidative stress, but data are still emerging. Side effects include nausea and rare low blood sugar in people on diabetes medicines.

6. Curcumin (from turmeric)
Curcumin is the main active compound in turmeric and has strong anti-inflammatory and antioxidant actions, blocking NF-κB and other inflammatory signals.[76] It may help general chronic pain and joint inflammation when taken with black pepper or in enhanced-absorption formulas. Typical supplemental doses range from 500–1,000 mg of curcumin per day. Side effects include stomach upset and interactions with blood thinners.

7. Coenzyme Q10 (CoQ10)
CoQ10 is involved in mitochondrial energy production and has antioxidant effects. In some chronic illness studies it reduced fatigue and improved cellular energy.[77] For CRPS, theory suggests better energy supply to nerves and muscles could support recovery, but specific trials are limited. Common supplemental doses are 100–300 mg/day taken with fat-containing food. Side effects are usually mild stomach upset.

8. B-complex vitamins (especially B1, B6, B12)
B vitamins support nerve repair, neurotransmitter production, and energy metabolism. Deficiencies can cause or worsen neuropathic pain.[78] Typical supplements may include B1 (thiamine), B6 (pyridoxine), and B12 (cobalamin) in low to moderate doses. In CRPS with poor diet or nerve injury, correcting deficiency may improve nerve health and reduce pain. Very high B6 doses over long periods can themselves cause nerve damage, so balanced formulas are important.

9. N-acetylcysteine (NAC)
NAC is a precursor of glutathione, one of the body’s main antioxidants, and also has anti-inflammatory and glutamate-modulating actions.[79] It has been studied in several psychiatric and pain conditions. Doses often range from 600–1,200 mg once or twice daily. In theory, NAC could reduce oxidative stress and abnormal glutamate signaling in CRPS, but direct evidence is still limited. Side effects include nausea and rare allergic reactions.

10. Resveratrol and polyphenol-rich extracts
Resveratrol (from grapes and berries) and other polyphenols have antioxidant and anti-inflammatory effects and may protect nerves in experimental models.[80] Supplements or high-polyphenol foods (berries, dark grapes, olives) might support overall anti-inflammatory balance in CRPS. Doses vary widely; side effects are usually mild but can include stomach upset and interaction with blood thinners.

---

Immunity-booster, regenerative, and stem-cell-related drugs

These medicines are not standard first-line CRPS treatments. Most are used only in severe, resistant cases or clinical trials and always under specialist care.

1. Intravenous immunoglobulin (IVIG)
IVIG is a pooled antibody product from many donors. It can modulate the immune system by neutralizing auto-antibodies and altering inflammatory cytokines.[81] Small early trials showed pain reduction with low-dose IVIG in refractory CRPS, but a later larger trial did not confirm benefit.[82] IVIG is given as slow intravenous infusion in hospital. Side effects include headache, flu-like symptoms, clotting risk, and kidney strain. It is expensive and reserved for research or highly selected cases.

2. Anti-TNF biologics (infliximab, etanercept)
As noted above, these drugs target TNF-α, a key inflammatory cytokine that is elevated in CRPS tissues.[83] Case series report improvements in pain and swelling in some severe patients who failed other therapies.[84] Dosing usually follows protocols for rheumatoid arthritis or bowel disease and is given by infusion or injection in hospital. Risks include serious infections, allergic reactions, and theoretical cancer risk, so they are used only in specialized settings.

3. Mesenchymal stem cell (MSC) therapy – experimental
Bone-marrow-derived mesenchymal stem cells can release anti-inflammatory and growth-promoting factors that may help repair nerve and vascular damage.[85] In animal models of CRPS, MSCs reduced pain behavior and changed nerve sodium channel expression.[86] Early human research programs are ongoing at major centers. Doses, routes, and long-term safety are still being studied, and MSC therapy is not yet an approved standard treatment for CRPS.

4. High-dose vitamin D as an immunomodulatory drug
When used at higher, prescription doses, vitamin D can be considered a drug rather than just a supplement. It influences many immune cells and cytokines.[87] In inflammatory and autoimmune diseases, correcting severe deficiency sometimes improves pain and fatigue. For CRPS, robust data are lacking, so doctors may correct deficiency but avoid extreme doses. Over-dosing can cause high calcium, kidney damage, and heart rhythm problems.

5. Growth-factor and neurotrophic-targeted experimental drugs
Some experimental medicines target nerve growth factor (NGF) or other growth pathways to reduce pain hypersensitivity and support nerve repair.[88] These are mostly in clinical trials for osteoarthritis and neuropathic pain, and may in future be studied in CRPS. They are not available for routine care and may have side effects like joint damage or immune reactions, so they remain research tools.

6. Combined regenerative programs (rehab + biological therapy)
Emerging research suggests that combining regenerative biologic treatments (such as stem-cell-based approaches or biologic drugs) with intensive rehabilitation might give the best results, because new or calmed tissues are immediately trained to function normally.[89] These programs are still experimental, often run in academic centers with strict inclusion criteria. Safety, long-term outcomes, and cost-effectiveness are still being studied.

---

Surgeries and interventional procedures

These are usually considered after good trials of non-drug and drug treatments. Decisions are made by a multidisciplinary pain team with the patient.

1. Spinal cord stimulation (SCS)
SCS involves placing thin electrodes in the epidural space near the spinal cord, connected to a small implanted battery.[90] The device sends gentle electrical pulses that change how pain signals are processed, often turning burning pain into a mild tingling or reducing it altogether. SCS is used for severe CRPS that has not improved with other treatments. Risks include infection, lead movement, and equipment problems.

2. Dorsal root ganglion (DRG) stimulation
DRG stimulation is similar to SCS but targets the nerve cell clusters (dorsal root ganglia) that carry pain signals from specific areas, such as the foot or hand.[91] It can give very focused relief for CRPS in one limb. Early studies suggest strong pain reduction and function improvement in many patients who respond. Risks are similar to SCS and include infection and lead displacement.

3. Sympathetic nerve blocks and sympathectomy
Sympathetic blocks involve injecting local anesthetic near sympathetic nerves, such as a stellate ganglion block for an arm or a lumbar sympathetic block for a leg.[92] If a block gives clear but temporary relief, more blocks or, rarely, a surgical or chemical sympathectomy (destroying part of the sympathetic chain) may be considered. Benefits include reduced pain and improved warmth and blood flow in responsive cases, but results are variable and there are risks of nerve or vascular injury.

4. Intrathecal drug delivery pump implantation
For very severe, widespread CRPS, a small pump can be implanted under the skin to deliver tiny doses of medicines (such as opioids, baclofen, or local anesthetics) directly into the spinal fluid.[93] This allows lower total drug doses with strong local effect. Surgery is complex and carries risks like infection, catheter problems, overdose or withdrawal if the pump fails, so it is reserved for very carefully selected patients.

5. Corrective orthopedic or soft-tissue surgery (last resort)
In late CRPS, some people develop fixed contractures, joint deformities, or severe tendon tightness. After careful assessment, orthopedic or plastic surgeons may perform tendon lengthening, joint release, or other procedures to restore a more functional position.[94] Surgery is risky in CRPS because new trauma can trigger flares, so it is only done when clear mechanical problems remain and always combined with intensive pre- and post-operative pain management and rehabilitation.

---

Prevention

1. Treat limb injuries early and properly – prompt fracture reduction, good cast fitting, and follow-up help reduce abnormal nerve and vascular responses.[95]

2. Encourage gentle movement soon after safe – as soon as doctors say it is safe, start light joint motion and physiotherapy to prevent stiffness and abnormal brain changes.[96]

3. Use vitamin C after certain fractures as advised – 500 mg daily for about 50 days after wrist fracture lowers CRPS risk in studies.[97]

4. Avoid overly tight casts or bandages – too much pressure can damage nerves and blood flow and may contribute to CRPS.

5. Control other health conditions – diabetes, vascular disease, and smoking all impair circulation and healing, increasing risk of complications.

6. Support good mental health – treating anxiety, depression, and high stress after injury may reduce chronic pain risk.

7. Educate about pain and normal healing – explaining that some pain is normal, but showing red-flag signs early, encourages timely review.

8. Avoid repeated unnecessary surgeries on the same limb – each procedure is another trauma and may raise CRPS risk.

9. Promote balanced diet, sleep, and movement – healthy lifestyle helps the immune and nervous systems recover after an injury.

10. Refer early to pain or rehab specialists if symptoms look like CRPS – early, expert treatment may stop progression and improve outcomes.[98]

---

When to see a doctor

A person should see a doctor urgently if, after an injury or surgery to a limb, they notice:

• Strong burning or deep pain that feels far worse than expected from the injury

• Swelling, shiny skin, or sweating changes in the limb

• Big temperature or color differences between the two limbs

• Increasing stiffness or difficulty moving fingers, hand, foot, or ankle

• Touch or light pressure feeling extremely painful

• Symptoms spreading up or down the limb or to another limb

They should see a pain specialist or neurologist when symptoms last more than a few weeks, keep getting worse, or do not improve with basic treatment. Early referral is especially important in children or teenagers, where early aggressive rehab often leads to better recovery.[99]

---

What to eat and what to avoid

1. Eat plenty of colorful fruits and vegetables – berries, leafy greens, tomatoes, and peppers provide antioxidants and polyphenols that help reduce inflammation and support blood vessels.[100]

2. Include fatty fish 2–3 times per week – salmon, mackerel, sardines, and trout supply omega-3 fats that lower inflammatory chemicals and may reduce chronic pain.[101]

3. Choose healthy fats – use extra-virgin olive oil, nuts, and seeds instead of butter or trans fats; these foods contain anti-inflammatory compounds like oleocanthal.[102]

4. Get enough lean protein – fish, poultry, eggs, beans, and lentils support muscle and tissue repair, especially when doing rehabilitation exercises.

5. Stay well hydrated – drinking enough water helps circulation and may reduce feelings of fatigue and brain fog.

6. Limit sugary drinks and refined sweets – high sugar can increase inflammation and weight gain, which worsen pain and mobility.

7. Cut down on processed and fast foods – many contain trans fats, excess salt, and additives that promote inflammation.

8. Avoid heavy alcohol use – alcohol can damage nerves, disturb sleep, and interact with many pain medicines.

9. Be careful with very high-dose supplements on your own – more is not always better, and some supplements can harm the liver, kidneys, or interact with drugs.

10. Work with a dietitian if weight or appetite are problems – professional advice can help maintain a healthy weight and ensure enough nutrients for healing.

---

FAQs

1. Is CRPS a “real” disease or just in the mind?
CRPS is very real. It involves changes in nerves, immune cells, and blood vessels in the affected limb and in the brain and spinal cord. However, stress and mood can strongly affect pain, so both body and mind need treatment.[103]

2. Can CRPS go away completely?
Some people, especially those diagnosed early and treated intensively, improve a lot or even recover fully. Others have long-term pain but can still improve function and quality of life with good management. Early treatment gives the best chance.

3. What is the difference between CRPS type I and type II?
Type I usually follows an injury without clear major nerve damage. Type II (formerly causalgia) happens when a major nerve is clearly injured. Symptoms are similar, and treatment principles are much the same.

4. Does every fracture or surgery lead to CRPS?
No. CRPS is rare compared to the number of injuries and surgeries. Certain events, such as distal radius fractures, seem to carry higher risk, but most people heal without CRPS. Vitamin C and early movement may reduce risk.

5. Is CRPS contagious or genetic?
CRPS is not contagious. You cannot catch it from someone else. There may be some genetic and immune factors that increase risk, but environment and injury play a big role.

6. Why does a light touch or breeze hurt so much?
In CRPS, pain nerves and spinal cord cells become very sensitive. Harmless touch signals are misread as pain (allodynia). Desensitization, nerve-targeted medicines, and brain training therapies can help reset this sensitivity over time.

7. Can children and teenagers get CRPS?
Yes. CRPS can occur in young people, often in a leg and sometimes after sports injuries. They often respond well to early, intensive physiotherapy and psychological support. Specialist pediatric pain teams are recommended.

8. Do I need strong opioids for CRPS?
Not usually. Modern CRPS guidelines try to avoid long-term strong opioids because benefits are limited and risks are high. Other medicines and therapies are preferred. Short-term opioid use may be considered only in severe cases under close supervision.

9. How long should I stay on medicines like gabapentin or pregabalin?
There is no fixed time. Doctors usually start low, increase slowly if helpful, and then re-check after weeks to months. If pain improves and stays stable, they may try a slow dose reduction. Stopping suddenly can cause withdrawal or symptom rebound, so changes must be gradual.

10. Are stem cell treatments for CRPS available now?
Stem-cell-based treatments for CRPS are still in the research phase. Animal studies and early human work are promising, but safety, dosing, and long-term effects are not fully known. At present they should only be accessed through regulated clinical trials, not commercial “miracle cure” clinics.

11. Can exercise make CRPS worse?
If exercise is too intense or sudden, it can flare pain. But carefully graded, regular movement supervised by a therapist usually helps in the long run. The key is starting at a safe level and increasing slowly, not avoiding movement altogether.

12. Is CRPS only in the limb, or can it affect the whole body?
CRPS mainly affects one limb, but over time it can spread to another limb or cause widespread symptoms like fatigue, sleep problems, and mood changes. This is because the whole nervous system becomes sensitized.

13. What happens if CRPS is not treated?
Without treatment, some people develop severe stiffness, muscle wasting, contractures, and permanent disability. Pain can spread and become more difficult to control. Early diagnosis and combined therapies are important to avoid this.

14. Can CRPS come back after it gets better?
Sometimes symptoms recur after a new injury, surgery, or major stress. People who had CRPS should tell doctors before any procedure so the team can plan careful pain control, early movement, and possible vitamin C prophylaxis.

15. Who should coordinate my CRPS care?
Ideally, a multidisciplinary pain clinic or rehabilitation team coordinates care. This usually includes a pain doctor, physiotherapist, occupational therapist, psychologist, and sometimes a surgeon or neurologist. They work together to create one clear plan, instead of many conflicting ones.

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: February 28, 2025.