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Complex Regional Pain Syndrome (CRPS)

(Reflex Sympathetic Dystrophy and Causalgia)


James C. Watson

, MD, Mayo Clinic College of Medicine and Science

Last full review/revision Feb 2020| Content last modified Feb 2020

Complex regional pain syndrome (CRPS) is chronic neuropathic pain that follows soft-tissue or bone injury (type I) or nerve injury (type II) and lasts longer and is more severe than expected for the original tissue damage. Other manifestations include autonomic changes (eg, sweating, vasomotor abnormalities), motor changes (eg, weakness, dystonia), and trophic changes (eg, skin or bone atrophy, hair loss, joint contractures). Diagnosis is clinical. Treatment includes drugs, physical therapy, and sympathetic blockade.

(See also Overview of Pain.)

CRPS type I was previously known as reflex sympathetic dystrophy (see also Complex Regional Pain Syndrome: Treatment Guidelines), and type II was known as causalgia. Both types occur most often in young adults and are 2 or 3 times more common among women.

Etiology of Complex Regional Pain Syndrome

CRPS type I typically follows an injury (usually of a hand or foot), most commonly after crush injuries, especially in a lower limb. It may follow amputation, acute myocardial infarction, stroke, or cancer (eg, lung, breast, ovary, central nervous system); no precipitant is apparent in about 10% of patients. It commonly occurs after immobilization of the limb to treat the initial injury.

CRPS type II is similar to type I but involves overt damage to a peripheral nerve.

Pathophysiology of CRPS

Pathophysiology is unclear, but peripheral nociceptor and central sensitization and release of neuropeptides (substance P, calcitonin gene-related peptide) help maintain pain and inflammation. The sympathetic nervous system is more involved in CRPS than in other neuropathic pain syndromes: Central sympathetic activity is increased, and peripheral nociceptors are sensitized to norepinephrine (a sympathetic neurotransmitter); these changes may lead to sweating abnormalities and poor blood flow due to vasoconstriction. Nonetheless, only some patients respond to sympathetic manipulation (ie, central or peripheral sympathetic blockade).

Symptoms and Signs of CRPS

Symptoms of complex regional pain syndrome vary greatly and do not follow a pattern; they include sensory, focal autonomic (vasomotor or sudomotor), and motor abnormalities.

Pain—burning or aching—is a core diagnostic feature. It does not follow the distribution of a single peripheral nerve; it is regional. It may worsen with changes in environment or emotional stress. Allodynia and/or hyperalgesia are usually present. Pain often causes patients to limit use of an extremity.

Cutaneous vasomotor changes (eg, red, mottled, or ashen color; increased or decreased temperature) and sudomotor abnormalities (dry or hyperhidrotic skin) may be present. Edema may be considerable and locally confined.

Other symptoms include trophic abnormalities (eg, shiny, atrophic skin; cracking or excess growth of nails; bone atrophy; hair loss) and motor abnormalities (weakness, tremors, spasm, dystonia with fingers fixed in flexion or equinovarus position of foot). Range of motion is often limited, sometimes leading to joint contractures. Symptoms may interfere with fitting a prosthesis after amputation.

Psychologic distress (eg, depression, anxiety, anger) is common, fostered by the poorly understood cause, lack of effective therapy, and prolonged course.

Diagnosis of CRPS

  • Clinical evaluation

Complex regional pain syndrome is diagnosed when the following are present:

  • Patients have continuing pain beyond that explained by dysfunction of a single nerve and that is disproportionate to any original tissue damage.
  • Certain clinical criteria (Budapest criteria [1]) are met.

The Budapest criteria have four categories. For CRPS to be diagnosed, the patient must report at least one symptom in three of the four categories, and the clinician must detect at least one sign in two of the same four categories (symptoms and signs overlap):

  • Sensory: Hyperesthesia (as a sign, to pinprick) or allodynia (as a sign, to light touch, deep somatic pressure, and/or joint movement)
  • Vasomotor: Temperature asymmetry (> 1° C as a sign) or asymmetric skin color changes
  • Sudomotor or edema: Sweating changes, sweating asymmetry, or edema
  • Motor or trophic: Trophic changes in skin, hair, or nails, decreased range of motion, or motor dysfunction (weakness, tremor, dystonia)

Also, there must be no evidence of another disorder that could explain the symptoms. If another disorder is present, CRPS should be considered possible or probable.

Bone changes (eg, demineralization on x-ray, increased uptake on a triple-phase radionuclide bone scan) may be detected and are usually evaluated only if the diagnosis is equivocal. However, on imaging tests, bone may also look abnormal after trauma in patients without CRPS, making the abnormalities nonspecific.

In one test of sympathetic involvement, a patient is given IV infusions of saline (placebo) or phentolamine 1 mg/kg over 10 minutes while pain scores are recorded; a decrease in pain after phentolamine but not placebo indicates sympathetically maintained pain.

Sympathetic nerve block (cervical stellate ganglion or lumbar) has been used for diagnosis (and is used for treatment). However, false-positive and false-negative results are common because not all CRPS pain is sympathetically maintained and nerve block may also affect nonsympathetic fibers.

Diagnosis reference

  • 1. Harden RN, Bruehl S, Stanton-Hicks M, Wilson PR: Proposed new diagnostic criteria for complex regional pain syndrome. Pain Med 8 (4):326–331, 2007.

Prognosis for CRPS

Prognosis varies and is difficult to predict. CRPS may remit or remain stable for years; in a few patients, it progresses, spreading to other areas of the body.

Treatment of CRPS

  • Multimodal therapy (eg, drugs, physical therapy, sympathetic blockade, psychologic treatments, neuromodulation, mirror therapy)

The primary goal of all treatments for complex regional pain syndrome is to increase the mobility of the affected limb.

Treatment of CRPS is complex and often unsatisfactory, particularly if begun late. It includes drugs, physical therapy, sympathetic blockade, psychologic treatments, and neuromodulation. Few controlled trials have been done.

Many of the drugs used for neuropathic pain, including tricyclic antidepressants, antiseizure drugs, and corticosteroids, may be tried; none is known to be superior. Long-term treatment with opioid analgesics may be useful for selected patients.

In some patients with sympathetically maintained pain, regional sympathetic blockade relieves pain, making physical therapy possible. Oral analgesics (nonsteroidal anti-inflammatory drugs [NSAIDs], opioids, various adjuvant analgesics) may also relieve pain sufficiently to allow rehabilitation.

For neuromodulation, implanted spinal cord stimulators are being increasingly used. Dorsal root ganglion stimulation may target localized symptoms. Transcutaneous electrical nerve stimulation (TENS), applied at multiple locations with different stimulation parameters, may be effective but requires a long trial.

Neuraxial infusion with opioids, anesthetics, ziconotide, and/or clonidine may help, and intrathecal baclofen may reduce dystonia.

Physical therapy is essential. Goals include desensitization, strengthening, increased range of motion, and vocational rehabilitation.

Desensitization of an allodynic limb is also essential. This procedure involves first applying stimuli that are relatively nonirritating (eg, silk) and, then over time, increasing to more irritating stimuli (eg, denim). Desensitization can also involve thermal contrast baths, in which the affected limb is placed in a cool water bath, then placed in a warm water bath.

Mirror therapy has been reported to benefit patients with CRPS type 1 due to phantom limb pain or stroke. Patients straddle a large mirror between their legs. The mirror reflects the image of the unaffected limb and hides the affected (painful or missing) limb, giving patients the impression that they have two normal limbs. Patients are instructed to move the normal limb while viewing its reflected image in the mirror. This exercise tricks the brain into thinking that the affected or absent limb is moving without pain. Most patients who do this exercise for 30 minutes a day for 4 weeks report a substantial reduction in pain.

Acupuncture may help relieve the pain.

Key Points

  • Complex regional pain syndrome may follow injury (to soft tissue, bone, or nerve), amputation, acute myocardial infarction, stroke, or cancer or have no apparent precipitant.
  • Diagnose CRPS if patients have neuropathic pain, allodynia or hyperalgesia, and focal autonomic dysregulation when no other cause is identified.
  • Prognosis is unpredictable, and treatment is often unsatisfactory.
  • Treat as early as possible using multiple modalities (eg, drugs used for neuropathic pain, physical therapy, sympathetic blockade, psychologic treatments, neuromodulation, mirror therapy).

More Information

  • Complex Regional Pain Syndrome: Treatment Guidelines

Drugs Mentioned In This Article

Drug Name Select Trade
phentolamine No US brand name
ziconotide PRIALT
calcitonin MIACALCIN
clonidine CATAPRES
baclofen LIORESAL

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