The autoimmune aetiology of unexplained chronic pain

Goebel, Andreas and Andersson, David and Helyes, Zsuzsanna and Clark, J David and Dulake, Debra (2022) The autoimmune aetiology of unexplained chronic pain. AUTOIMMUNITY REVIEWS, 21 (3). ISSN 1568-9972

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Abstract

Chronic pain is the leading cause of life years lived with disability worldwide. The aetiology of most chronic pain conditions has remained poorly understood and there is a dearth of effective therapies. The WHO ICD-11 has categorised unexplained chronic pain states as 'chronic primary pains' (CPP), which are further defined by their association with significant distress and/or dysfunction. The new mechanistic term, 'nociplasticic pain' was developed to illustrate their presumed generation by a structurally intact, but abnormally functioning nociceptive system. Recently, researchers have unravelled the surprising, ubiquitous presence of pain-sensitising autoantibodies in four investigated CPP indicating autoimmune causation. In persistent complex regional pain syndrome, fibromyalgia syndrome, chronic post-traumatic limb pain, and non-inflammatory joint pains associated with rheumatoid arthritis, passive transfer experiments have shown that either IgG or IgM antibodies from patient-donors cause symptoms upon injection to rodents that closely resemble these clinical disorders. Targets of antibody-binding and downstream effects vary between conditions, and more research is needed to elucidate the details. The central nervous system appears largely unaffected by antibody binding suggesting that the clinically evident CNS symptoms associated with CPP might arise downstream. In this narrative review pertinent findings are described, and it is suggested that additional symptom-based disorders might be examined for the contribution of antibody-mediated autoimmune mechanisms.

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