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Severe pain and disability are common among those with chronic forms of this condition. Accumulating evidence suggests that CRPS may involve both autoinflammatory and autoimmune components. In this review article, evidence for dysfunction of both the innate and adaptive immune systems in CRPS is presented. Findings from human studies in which cytokines and other inflammatory mediators were measured in the skin of affected limbs are discussed. Additional results from studies of mediator levels in animal models are evaluated in this context. Similarly, the evidence from human, animal, and translational studies of the production of autoantibodies and the potential targets of those antibodies is reviewed. Compelling evidence of autoinflammation in skin and muscle of the affected limb has been collected from CRPS patients and laboratory animals. Cytokines including IL-1\u03b2, IL-6, TNF\u03b1, and others are reliably identified during the acute phases of the syndrome. More recently, autoimmune contributions have been suggested by the discovery of self-directed pain-promoting IgG and IgM antibodies in CRPS patients and model animals. Both the autoimmune and the autoinflammatory components of CRPS appear to be regulated by neuropeptide-containing peripheral nerve fibers and the sympathetic nervous system. While CRPS displays a complex neuroimmunological pathogenesis, therapeutic interventions could be designed targeting autoinflammation, autoimmunity, or the neural support for these phenomena.<\/jats:p>","DOI":"10.1177\/1744806918799127","type":"journal-article","created":{"date-parts":[[2018,8,20]],"date-time":"2018-08-20T06:01:31Z","timestamp":1534744891000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":71,"title":["Autoinflammatory and autoimmune contributions to complex regional pain syndrome"],"prefix":"10.1177","volume":"14","author":[{"given":"J","family":"David Clark","sequence":"first","affiliation":[{"name":"Anesthesiology Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA"},{"name":"Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivianne 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