The autoimmune aetiology of unexplained chronic pain

TY - JOUR

T1 - The autoimmune aetiology of unexplained chronic pain

AU - Goebel, Andreas

AU - Andersson, David

AU - Helyes, Zsuzsanna

AU - Clark, David

AU - Dulake, Debra

AU - Svensson, Camilla

N1 - Funding Information: This work was funded by internal sources. AG has been supported by the Pain Relief Foundation, Liverpool UK. ZH was supported by Hungarian research grant OTKA K138046 , National Brain Research Program and Thematic Excellence Program 2021 of the Ministry of Innovation and Technology (Hungary) and the Eotvos Lorand Research Network. JCD was supported by the NIH award NS117340. Publisher Copyright: © 2021 Elsevier B.V.

PY - 2022/3

Y1 - 2022/3

N2 - 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

AB - 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

KW - Primary chronic pain

KW - Fibromyalgia syndrome

KW - Complex regional pain syndrome

KW - Rheumatoid arthritis

KW - Autoantibody

KW - Passive immunoglobulin transfer

UR - http://www.scopus.com/inward/record.url?scp=85121302310&partnerID=8YFLogxK

U2 - 10.1016/j.autrev.2021.103015

DO - 10.1016/j.autrev.2021.103015

M3 - Review article

SN - 1568-9972

VL - 21

JO - AUTOIMMUNITY REVIEWS

JF - AUTOIMMUNITY REVIEWS

IS - 3

M1 - 103015

ER -