Complex regional pain syndrome – Autoimmune or functional neurologic syndrome

Christopher Chang, Patrick McDonnell, M. Eric Gershwin

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations


Complex regional pain syndrome (CRPS) purports to explain extremity pain accompanied by a variety of subjective complaints, including sensitivity to touch, fatigue, burning sensations, allodynia and signs consistent with voluntary immobilization, including skin changes, edema and trophic changes. By its own definition, CRPS pain is disproportionate to any inciting event or underlying pathology, which means that the syndrome describes non-anatomic and exaggerated symptoms. Although CRPS was coined in the early 1990s, physicians have described unexplained exaggerated pain for centuries. Before a small group of researchers assigned this historical phenomenon with the name CRPS, other physicians in various subspecialties investigated the existence of a common pathophysiologic mechanism but found none. The literature was searched for evidence of a reproducible pathologic mechanism for CRPS. Although some have suggested that CRPS is an autoimmune disease, there is a paucity of evidence to support this. While cytokines such as IL-1β, IL-6 and TNF-α have been detected during the early phases of CRPS, this cannot lead to the conclusion that CRPS is an autoimmune disease, nor that it is an autoinflammatory disorder. Moreover, intravenous immunoglobulin has showed inconsistent results in the treatment of CRPS. On the other hand, CRPS has been found to meet at least three out of four criteria of malingering, which was previously a DSM-IV diagnosis; and its diagnostic criteria are virtually identical to current DSM-5 Functional Neurological Disorder (“FND”), and proposed ICD-11 classification, which includes FND as a distinct neurological diagnosis apart from any psychiatric condition. Unfortunately, the creation of CPRS is not merely misguided brand marketing. It has serious social and health issues. At least in part, the existence of CRPS has led to the labeling of many patients with a diagnosis that allows the inappropriate use of invasive surgery, addictive opioids, and ketamine. The CRPS hypothesis also ignores the nature and purpose of pain, as a symptom of some organic or psychological process. Physicians have long encountered patients who voice symptoms that cannot be biologically explained. Terminology historically used to describe this phenomenon have been medically unexplained symptoms (“MUS”), hysterical, somatic, non-organic, psychogenic, conversion disorder, or dissociative symptoms. The more recent trend describes disorders where there is a functional, rather than structural cause of the symptoms, as “functional disorders.” Physicians report high success treating functional neurological symptoms with reassurance, physiotherapy, and cognitive behavior therapy measured in terms of functional improvement. The CRPS label, however, neither leads to functional improvement in these patients nor resolution of symptoms. Under principles of evidence-based medicine, the CRPS label should be abandoned and the syndrome should simply be considered a subset of FNDs, specifically Functional Pain Disorder; and treated appropriately.

Original languageEnglish (US)
Article number100080
JournalJournal of Translational Autoimmunity
StatePublished - Jan 2021
Externally publishedYes


  • Addiction
  • Autoimmune
  • Intravenous immunoglobulin
  • Opioids
  • Pain management
  • Reflex sympathetic dystrophy

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy


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