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Pain Medicine

Complex Regional Pain Syndrome

Complex Regional Pain Syndrome · G90.50

Complex regional pain syndrome (CRPS) is a chronic pain condition that develops after trauma or nerve injury, characterized by persistent pain disproportionate to the inciting stimulus, autonomic dysfunction (skin temperature and color changes, sweating abnormalities), motor dysfunction, and trophic changes (edema, skin, hair, and nail abnormalities).

2026-03-28

At a Glance

CRPS was formerly known as reflex sympathetic dystrophy (RSD) or causalgia. It is characterized by disproportionately severe persistent pain following trauma, accompanied by autonomic dysfunction and motor impairment in the affected limb. The incidence is reported at approximately 5-26 per 100,000 population, and it is approximately 3-4 times more common in women [1]. Early diagnosis and multidisciplinary treatment are critical for prognosis.

Definition and Overview

Complex regional pain syndrome (CRPS) is a chronic pain condition that persists beyond the normally expected healing time following trauma, surgery, or nerve injury. The intensity and duration of pain are disproportionate to the inciting stimulus, accompanied by autonomic dysfunction, motor impairment, and trophic changes [4].

CRPS Type I occurs without definite nerve injury and was formerly known as reflex sympathetic dystrophy (RSD). CRPS Type II develops after direct peripheral nerve injury and was formerly known as causalgia.

The incidence is approximately 5-26 per 100,000 population [1], and it is approximately 3-4 times more common in women. It occurs slightly more frequently in the upper extremity (after wrist fracture) than the lower extremity.

Etiology

Neuroinflammation

Following trauma, sustained release of neuropeptides such as Substance P and CGRP from peripheral sensory nerves induces vasodilation, edema, and inflammation. This neurogenic inflammation persists abnormally even after the normal tissue healing response.

Central Sensitization

Persistent input of peripheral pain signals sensitizes pain-processing neurons in the spinal dorsal horn (central sensitization), producing excruciating pain even from mild stimuli [4]. Reorganization of the brain's pain processing circuits and body schema also contributes to the sensory and motor abnormalities of CRPS.

Sympathetic Nervous System Overactivation

Abnormal sympathetic nerve activity in the affected limb contributes to pain maintenance. Abnormal sensitivity of peripheral sensory nerves to norepinephrine develops, and in some cases sympathetically maintained pain (SMP) -- worsening of pain upon sympathetic activation -- is observed.

Symptoms

Budapest Diagnostic Criteria [2]

The official diagnostic criteria for CRPS are the Budapest Criteria (2010).

Clinical diagnostic criteria: Symptoms must be present in at least 3 of the following 4 categories, and signs in at least 2.

1. Sensory: Allodynia, hyperalgesia -- symptoms or signs
2. Vasomotor: Skin temperature asymmetry, skin color changes -- symptoms or signs
3. Sudomotor/edema: Sweating abnormalities, limb edema -- symptoms or signs
4. Motor/trophic: Decreased range of motion, motor dysfunction (tremor, dystonia, weakness), trophic changes (hair, nails, skin) -- symptoms or signs

The condition must not be better explained by another diagnosis.

Stages

  • Acute stage (weeks to months): Pain, edema, skin warmth and erythema
  • Dystrophic stage (months to years): Decreased edema, skin cooling, skin and hair changes
  • Atrophic stage (years): Skin atrophy, joint contracture, osteoporosis

Treatment

Physical Therapy and Occupational Therapy

Physical therapy plays a central role in CRPS treatment. Desensitization training that gradually activates the affected limb within the pain tolerance range and graded motor imagery (GMI) are effective.

Research has shown that graded motor imagery therapy significantly improved pain intensity and function in long-standing CRPS patients [3].

Pharmacological Treatment

  • Nonsteroidal anti-inflammatory drugs (NSAIDs): Acute phase pain and inflammation control
  • Pregabalin, gabapentin: Neuropathic pain control
  • Antidepressants (amitriptyline, duloxetine): Central sensitization and pain control
  • Bisphosphonates: Reduction of bone resorption, with pain improvement reported in some studies
  • Corticosteroids: Short-term use during the acute inflammatory stage

Nerve Block Therapy

Sympathetic nerve blocks are used in CRPS patients with confirmed SMP to relieve pain and enhance participation in physical therapy. Stellate ganglion block is performed for upper extremity CRPS, and lumbar sympathetic block for lower extremity CRPS [5].

Spinal Cord Stimulation (SCS)

There is evidence that spinal cord stimulation is effective for long-term pain control in chronic CRPS refractory to conservative treatment.

Frequently Asked Questions

The pathogenesis of CRPS has not been fully elucidated, but abnormally persistent neuroinflammation after tissue injury, central sensitization, sympathetic nervous system overactivation, and immune response abnormalities act in combination [4]. Trauma severity does not always correlate with CRPS risk, and it can occur even after minor sprains.

CRPS Type I (formerly RSD) occurs without identifiable nerve injury. CRPS Type II (formerly causalgia) occurs after definite peripheral nerve injury. Clinical presentation and treatment approaches are similar between the two types.

It is characterized by persistent burning and stabbing pain. Allodynia -- excruciating pain from light stimuli such as clothing brushing against skin -- and hyperalgesia -- excessive response to painful stimuli -- are present. The affected limb differs in temperature from the opposite limb, with color changes (redness or cyanosis), edema, and sweating abnormalities.

Starting aggressive rehabilitation and treatment early can prevent chronification. The longer pain and autonomic dysfunction persist, the stronger central sensitization becomes, making treatment more difficult. Early physical therapy, pain management, and education are critical for improving prognosis [4].

In upper extremity CRPS with sympathetically maintained pain, stellate ganglion block can help reduce pain and improve circulation. Rehabilitation outcomes are enhanced when physical therapy is combined following the block. Some CRPS cases do not respond to sympathetic blockade (sympathetically independent pain), so the procedure also serves a diagnostic purpose to assess treatment responsiveness.

Avoiding use of the affected limb due to pain worsens atrophy and sensitization. Physical therapy and occupational therapy that gradually use the limb within the pain tolerance range are important. Mirror therapy and graded motor imagery help normalize the central nervous system's body map [3].

References

  1. [1] de Mos M, de Bruijn AG, Huygen FJ, Dieleman JP, Stricker BH, Sturkenboom MC (2007). "The incidence of complex regional pain syndrome: a population-based study." Pain, 129: 12-20. DOI PubMed
  2. [2] Harden RN, Bruehl S, Perez RS, Birklein F, Marinus J, Maihofner C, Lubenow T, Buvanendran A, Mackey S, Graciosa J (2010). "Validation of proposed diagnostic criteria (the 'Budapest Criteria') for complex regional pain syndrome." Pain, 150: 268-274. DOI PubMed
  3. [3] Moseley GL (2004). "Graded motor imagery is effective for long-standing complex regional pain syndrome: a randomised controlled trial." Pain, 108: 192-198. DOI PubMed
  4. [4] Birklein F, O'Neill D, Schlereth T (2015). "Complex regional pain syndrome: an optimistic perspective." Neurology, 84: 89-96. DOI PubMed
  5. [5] Meier PM, Zurakowski D, Berde CB, Sethna NF (2009). "Lumbar sympathetic blockade in children with complex regional pain syndromes: a double blind placebo-controlled crossover trial." Anesthesiology, 111: 372-380. DOI PubMed

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