• Disease Overview
  • Synonyms
  • Subdivisions
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
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Complex Regional Pain Syndrome


Last updated: 2/8/2023
Years published: 1986, 1987, 1994, 1995, 1996, 1997, 1998, 1999, 2000, 2004, 2007, 2019, 2023


NORD gratefully acknowledges Alexander Pham, NORD Editorial Intern from the Massachusetts College of Pharmacy and Health Sciences, and Stephen Bruehl, PhD, Professor of Anesthesiology, Vanderbilt University Medical Center, for assistance in the preparation of this report.

Disease Overview


Complex regional pain syndrome (CRPS) is a disorder in which pain, occurring spontaneously or from a sensory stimulus, is disproportionately far more painful than it should be. An example of this would be light touching of the skin, which normally is not painful, yet is perceived as extremely painful in CRPS patients. The disproportionate pain is also reflected in normally painful stimuli, such as a pinprick, hurting more than it should (hyperalgesia). CRPS usually affects one limb after a limb injury or surgery. Usually, patients with CRPS will experience limited use of their affected limbs due to the pain. Besides increased perception of pain, other signs and symptoms that are seen with CRPS particularly in its early stages are a warm, red and swollen extremity on the affected side. In its later stages, a cool, bluish and sweaty limb is common. CRPS is often treated with physical and occupational therapy, and the patient will typically require medications or other interventions to manage the pain.


CRPS has traditionally been subdivided into 2 categories: type I and type II CRPS. In CRPS type I, there are no nerve injuries or lesions identified. CRPS type I is also known as “reflex sympathetic dystrophy,” and it comprises about 90 percent of all cases of CRPS. CRPS type II (causalgia), on the other hand, is diagnosed when there is evidence of nerve damage. A new CRPS subdivision has recently been added: CRPS with remission of some features. This label applies to patients who have met the full CRPS diagnostic criteria detailed below in the past, but who currently display insufficient CRPS features to meet the full criteria (i.e., ongoing CRPS-related pain and features but with some improvement).

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  • CRPS
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  • CRPS type I (reflex sympathetic dystrophy)
  • CPRS type II (causalgia)
  • CRPS with remission of some features
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Signs & Symptoms

The most common and prominent symptom of CRPS is the pain that affected individuals will feel. The pain is often deep inside the limbs with a burning, stinging or tearing sensation. Sensory changes are also common, and may include increased sensitivity to painful stimuli, feeling pain from stimuli that are usually non-painful and, in some instances, sensory loss (e.g., numbness).

In addition to pain, patients commonly experience an affected extremity that is warm, red and swollen, at least initially. In many patients, as CRPS continues, the affected extremity may more often feel cool with dark or bluish skin. Swelling, resulting from fluid build-up in the limb (edema), can be present regardless of the color and temperature of the skin, but is typically more prominent with the early clinical picture (red and warm skin). Skin color and temperature may sometimes change even over short periods of time inconsistently. In addition to the changes above, CRPS patients may experience skin that becomes thin and shiny and may experience either increased or decreased hair and nail growth in the affected extremity.

Most patients will experience motor impairment, which is the decrease in the ability to use the limbs for movement, with weakness or limited range of motion being the most common impairments. The impairments may be seen in a reduction in strength in handgrip or during tiptoe-standing. Some patients may develop spasms or even uncontrollable muscle contractions (dystonia).

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The exact causes of CRPS are unclear, but it is likely that there are multiple factors that contribute to its development.

Immobilization (e.g., casting) to keep a limb from moving in order to allow it heal is a common treatment for injuries such as broken bones or fractures in the limb. In adults and pediatric patients, CRPS type I was commonly seen in those who have a history of immobilization, and this was associated with a worsening of symptoms. Immobilization of limbs in patients after fractures or surgery results in an increase in sensitivity to pain, edema and temperature increase in the affected limb. This suggests that immobilization may play a role in the development of the disease.

CRPS may also be caused in part by alterations to the nervous system of the body. One part of the nervous system is the sympathetic nervous system. The sympathetic nervous system is activated in “fight or flight” situations, which are times when the body is in high level of stress and requires alertness. During times of stress, the sympathetic nervous system constricts blood vessels to reduce blood flow to the extremities. In contrast, low sympathetic nervous system activity increases blood flow to the extremities. In CRPS, sympathetic function may initially be decreased, which could contribute to warm, red and swollen limbs. The sympathetic nervous system may also play a role in contributing to the pain associated with CRPS. Although it is believed that the sympathetic nervous system in CRPS may become linked to pain receptors, it is still unclear exactly how the sympathetic nervous system causes pain in patients with CRPS.

Inflammation may also play a significant role in the development of the syndrome. In CRPS, particularly in its early stages, it is found that patients have increased levels of inflammation-causing substances (cytokines) released by the body. Along with the inflammatory cytokines, there are pain-enhancing substances in the nerves that are released. The increased inflammatory and pain-producing substances in CRPS are a possible explanation for why a person with CRPS may experience pain from a stimulus that normally should not cause pain.

It is possible that genetic factors may contribute to CRPS; however, there is no clear genetic risk pattern known at this time. There are a few genes that may contribute to CRPS, but the ones most frequently identified are in genes that influence the immune system and inflammation. It is possible that particular genetic variants that a person is born with might increase the risk of developing CRPS after injury, but there is no evidence that CRPS is a disease that can be caused by genetic factors alone.

Psychological factors, such as anxiety, depression and anger, may worsen the symptoms of CRPS. In children, psychological issues are often assumed to play a greater role in CRPS than in adults, but this belief remains unproven.

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Affected populations

CRPS occurs 3 to 4 times more often in women than men. Although CRPS can occur at any age, it is rare in children and adolescents. In the pediatric population, the onset of CRPS usually occurs in early adolescence with the lower end of the range falling between 7 to 9 years. In adults, the age of onset is highly variable from 37 to 70 years of age. CRPS occurs most frequently in people of European ancestry (in about 66 to 80 percent of cases). In a study done in the United States, it was found that CRPS type I developed in 5.46 persons out of every 100,000 per year. It is estimated that CRPS affects nearly 200,000 patients annually in the United States.

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Diagnosis of CRPS is suspected when a patient’s symptoms develop 4 to 6 weeks after limb trauma, symptoms cannot be fully explained by the initial trauma and the symptoms are regional (affecting an entire limb). Actual diagnosis of CRPS is made solely based on a history and physical examination to determine whether a patient meets CRPS diagnostic criteria (often called the “Budapest criteria”).

The Budapest criteria has 4 components. First, the patient has continuing pain of an intensity disproportionate to any event that provokes it. Second, the patient must report symptoms in at least 3 of the 4 following categories: sensory (increased in sensitivity), vasomotor (temperature or color changes in the skin of affected limb), sudomotor/edema (sweating changes or swelling) and motor/trophic (motor impairment or changes in the hair/nails/skin). Third, the patient must also exhibit signs, which are observable by the health care provider, in at least 2 of the 4 categories above (sensory, vasomotor, sudomotor/edema, motor/trophic). The last component of the Budapest criteria is that no other diagnosis can better explain the signs and symptoms. The Budapest criteria have recently been incorporated into the new ICD-11 international diagnostic coding system.

There is no “gold standard” test for diagnosing CRPS, and the diagnosis can be made with no testing at all other than the examination by a medical professional. Bone scans (bone scintigraphy) are sometimes used to support a CRPS diagnosis, but they are not required. Diagnostic sympathetic blocks, while also not required for diagnosis, are sometimes used to help determine the degree to which sympathetic nerve activity is contributing to the CRPS pain.

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Standard Therapies


CRPS is best treated using multiple approaches simultaneously, including physical therapy (PT), occupational therapy (OT), medications and interventional procedures and pain-focused psychological therapy. The goal of treatment is to manage the pain and to increase mobility of the affected limbs.

Physical and Occupational Therapy

PT and OT are considered first-line treatments for CRPS. Some available therapeutic methods that can be used include desensitization, strength and flexibility training, vocational support, coping skills training, postural control, gait retraining, enhancing ability to carry out daily activities and relaxation techniques. Another possible rehabilitation method that can be used is graded motor imagery. This method is used to train the brain to enhance motor coordination and function of the limbs that are affected. There are few downsides to PT and OT for CRPS, except for cost and convenience, and it is suggested that a patient newly diagnosed with CRPS should seek out PT and OT care.

Pharmacologic Therapy

Pain is a major concern with CRPS, and this can be managed with a variety of medications that can reduce and control the pain. Pain management is important so that a patient with CRPS can undergo PT with minimal pain.

Anticonvulsants may be useful in treating pain that is associated with damage or injury to nerves (neuropathic pain). Drugs such as gabapentin and pregabalin are options for treating neuropathic pain and are often used in management of CRPS. These drugs have modest effects for the reduction of pain. Topical creams containing lidocaine (a numbing agent) can also be used for neuropathic pain.

Another standard treatment for CRPS is certain types of antidepressant drugs, even if a patient is not depressed. These drugs cause chemical changes in the brain that may help reduce pain and also improve sleep, a common problem among CRPS patients.

Bisphosphonates may be beneficial in patients with CRPS. Bisphosphonates work by inhibiting the breakdown of bones by cells called osteoclasts; however, it is unlikely that bisphosphonates help with CRPS pain by this mechanism. Regardless of the mechanism of action, bisphosphonates, such as alendronate, have shown some signs of efficacy in reducing CRPS pain, particularly in its earlier stages, although they are not widely used in CRPS treatment at the present time.

Glucocorticoids (steroid medications) are another treatment option for CRPS. There is some evidence that they may be effective at least in the early stages of CRPS (less than a year). In patients who have had CRPS for a longer duration (chronic CRPS), glucocorticoid treatments may have no beneficial effects.

Opioids may also be used for CRPS; however, there are very few studies that have investigated the use of opioids for CRPS. The studies that have been done with opioids do not show that they are effective. The use of opioids may be considered if other options have failed, although opioid medications may carry significant risks.

Interventional Procedures

Certain procedures may be required for those who find noninvasive treatments, such as medications and PT, ineffective.

Sympathetic nerve blockade can be used to block the nerves of the sympathetic nervous system. With this nerve blockade, local anesthetics, such as lidocaine, are injected to block the nerves, which may result in a decrease in pain sensation for some patients. There is little research evidence to show its benefits for CRPS as a whole, but it has been reported to work and be life-changing in some patients.

Spinal cord stimulation (SCS) may be beneficial for patients who have not adequately responded to the interventions above. SCS uses an electric pulse stimulation to control the transmission of pain signals in the spinal cord. This treatment is relatively safe and reversible but may be expensive.

Pain-Focused Psychological Therapy

For individuals in whom CRPS does not quickly resolve with the noninvasive treatments above, psychological issues frequently emerge resulting from life disruptions related to CRPS and the fact that psychological stress and emotional distress often exacerbate CRPS pain. Psychological therapy focused on addressing barriers to living with CRPS and learning strategies to manage symptoms (e.g., mindfulness techniques, relaxation and imagery training, biofeedback) may be useful for enhancing quality of life in those living with CRPS. This type of psychological therapy typically employs cognitive behavioral and/or mindfulness training techniques.

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Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Some current clinical trials also are posted on the following page on the NORD website:

For information about clinical trials sponsored by private sources, contact: www.centerwatch.com

For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/

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Ott S, Maihofner C. Signs and symptoms in 1,043 patients with complex regional pain syndrome. J Pain. 2018;19(6):599-611. https://www.ncbi.nlm.nih.gov/pubmed/29409933

Kriek N, Schreurs MWJ, Groeneweg JG, et al. Spinal cord stimulation in patients with complex regional pain syndrome: a possible target for immunomodulation? Neuromodulation. 2018;21(1):77-86. https://www.ncbi.nlm.nih.gov/pubmed/29064599

Colloca L, Ludman T, Bouhassira D, et al. Neuropathic pain. Nat Rev Dis Primers. 2017;3:17002. https://www.ncbi.nlm.nih.gov/pubmed/28205574

Bruehl S. Complex regional pain syndrome. BMJ. 2015;351:h2730. https://www.ncbi.nlm.nih.gov/pubmed/26224572

Kumar A, Maitra S, Khanna P, Baidya DK. Clonidine for management of chronic pain: A brief review of the current evidences. Saudi J Anaesth. 2014;8(1):92-96. https://www.ncbi.nlm.nih.gov/pubmed/24665248

Jensen TS, Finnerup NB. Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms. Lancet Neurol. 2014;13(9):924-935. https://www.ncbi.nlm.nih.gov/pubmed/25142459

Borchers AT, Gershwin ME. Complex regional pain syndrome: a comprehensive and critical review. Autoimmun Rev. 2014;13(3):242-265. https://www.ncbi.nlm.nih.gov/pubmed/24161450

Perez RS, Zollinger PE, Dijkstra PU, et al. Evidence based guidelines for complex regional pain syndrome type 1. BMC Neurol. 2010;10:20. https://www.ncbi.nlm.nih.gov/pubmed/20356382

Drake MT, Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc. 2008;83(9):1032-1045. https://www.ncbi.nlm.nih.gov/pubmed/18775204

McCorry LK. Physiology of the autonomic nervous system. Am J Pharm Educ. 2007;71(4):78. https://www.ncbi.nlm.nih.gov/pubmed/17786266

Taskaynatan MA, Balaban B, Karlidere T, Ozgul A, Tan AK, Kalyon TA. Factitious disorders encountered in patients with the diagnosis of reflex sympathetic dystrophy. Clin Rheumatol. 2005;24(5):521-526. https://www.ncbi.nlm.nih.gov/pubmed/16010448

Abdi S. Complex regional pain syndrome in adults: pathogenesis, clinical manifestations, and diagnosis. Updated July 12, 2022. https://www.uptodate.com/contents/complex-regional-pain-syndrome-in-adults-pathogenesis-clinical-manifestations-and-diagnosis. Accessed Dec 7, 2022.

Sherry DD. Complex regional pain syndrome in children. Updated January 14, 2022. https://www.uptodate.com/contents/complex-regional-pain-syndrome-in-children. Accessed Dec 7, 2022.

Neuro Orthopaedic Institute. Graded Motor Imagery. Graded Motor Imagery. Published n.d. https://www.gradedmotorimagery.com/. Accessed Dec 7, 2022.

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