Pain: A Review of Interleukin-6 and Its Roles in the Pain of Rheumatoid Arthritis

Anthony Sebba Division of Rheumatology, University of South Florida, Tampa, FL, USACorrespondence: Anthony SebbaDivision of Rheumatology, University of South Florida, 13220 USF Laurel Drive, Tampa, FL, 33612, USATel +1 727 773 9793Fax +1 727 773 0674Email anthonysebba@gmail.comAbstract: Pain is a ma...

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Autor principal:	Sebba A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	animal model noninflammatory preclinical Diseases of the musculoskeletal system RC925-935
Acceso en línea:	https://doaj.org/article/cc0cb8149d6243feb3c59eb4d6cfdddf
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spelling	oai:doaj.org-article:cc0cb8149d6243feb3c59eb4d6cfdddf2021-12-02T14:20:30ZPain: A Review of Interleukin-6 and Its Roles in the Pain of Rheumatoid Arthritis1179-156Xhttps://doaj.org/article/cc0cb8149d6243feb3c59eb4d6cfdddf2021-03-01T00:00:00Zhttps://www.dovepress.com/pain-a-review-of-interleukin-6-and-its-roles-in-the-pain-of-rheumatoid-peer-reviewed-article-OARRRhttps://doaj.org/toc/1179-156XAnthony Sebba Division of Rheumatology, University of South Florida, Tampa, FL, USACorrespondence: Anthony SebbaDivision of Rheumatology, University of South Florida, 13220 USF Laurel Drive, Tampa, FL, 33612, USATel +1 727 773 9793Fax +1 727 773 0674Email anthonysebba@gmail.comAbstract: Pain is a major and common symptom reported as a top priority in patients with rheumatoid arthritis (RA). Intuitively, RA-related pain is often considered to be a natural consequence of peripheral inflammation, so treatment of RA is expected to manage pain concurrently as part of inflammation control. However, pain in patients with RA can be poorly correlated with objective measures of inflammation, for example, in patients who are otherwise in remission. Joint damage appears to account for only a fraction of this residual pain. Emerging evidence suggests that alteration of peripheral and central pain processing contributes to RA-related pain; this is parallel to, but somewhat independent of, joint inflammation. Interleukin (IL)-6 is a proinflammatory cytokine that contributes to the pathogenesis of RA. It exerts systemic effects via signaling through soluble forms of the IL-6 receptor (“trans-signaling”). Evidence from preclinical studies demonstrates that intra-articular IL-6 can produce long-lasting peripheral sensitization to mechanical stimulation and suggests an important role for IL-6 in central pain sensitization. This may be partly explained by its ability to activate neurons through trans-signaling, affecting nociceptive plasticity and nerve fiber regrowth. Local activity at neuron endings may culminate in altered pain processing in the central nervous system because of persistent signaling from sensitized peripheral neurons. Peripheral and central sensitization can promote the development of chronic pain, which can have a significant impact on patients’ health and quality of life. A proportion of pain in RA may be more appropriately managed as an entity separate from inflammation. Both the peripheral and central nervous systems should be recognized as important potential systems targeted by RA. The substantial burden of RA-related chronic pain suggests that pain should be a key focus in RA management and should be assessed and addressed early and separately from the inflammatory component.Keywords: animal model, non-inflammatory, preclinicalSebba ADove Medical Pressarticleanimal modelnoninflammatorypreclinicalDiseases of the musculoskeletal systemRC925-935ENOpen Access Rheumatology: Research and Reviews, Vol Volume 13, Pp 31-43 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	animal model noninflammatory preclinical Diseases of the musculoskeletal system RC925-935
spellingShingle	animal model noninflammatory preclinical Diseases of the musculoskeletal system RC925-935 Sebba A Pain: A Review of Interleukin-6 and Its Roles in the Pain of Rheumatoid Arthritis
description	Anthony Sebba Division of Rheumatology, University of South Florida, Tampa, FL, USACorrespondence: Anthony SebbaDivision of Rheumatology, University of South Florida, 13220 USF Laurel Drive, Tampa, FL, 33612, USATel +1 727 773 9793Fax +1 727 773 0674Email anthonysebba@gmail.comAbstract: Pain is a major and common symptom reported as a top priority in patients with rheumatoid arthritis (RA). Intuitively, RA-related pain is often considered to be a natural consequence of peripheral inflammation, so treatment of RA is expected to manage pain concurrently as part of inflammation control. However, pain in patients with RA can be poorly correlated with objective measures of inflammation, for example, in patients who are otherwise in remission. Joint damage appears to account for only a fraction of this residual pain. Emerging evidence suggests that alteration of peripheral and central pain processing contributes to RA-related pain; this is parallel to, but somewhat independent of, joint inflammation. Interleukin (IL)-6 is a proinflammatory cytokine that contributes to the pathogenesis of RA. It exerts systemic effects via signaling through soluble forms of the IL-6 receptor (“trans-signaling”). Evidence from preclinical studies demonstrates that intra-articular IL-6 can produce long-lasting peripheral sensitization to mechanical stimulation and suggests an important role for IL-6 in central pain sensitization. This may be partly explained by its ability to activate neurons through trans-signaling, affecting nociceptive plasticity and nerve fiber regrowth. Local activity at neuron endings may culminate in altered pain processing in the central nervous system because of persistent signaling from sensitized peripheral neurons. Peripheral and central sensitization can promote the development of chronic pain, which can have a significant impact on patients’ health and quality of life. A proportion of pain in RA may be more appropriately managed as an entity separate from inflammation. Both the peripheral and central nervous systems should be recognized as important potential systems targeted by RA. The substantial burden of RA-related chronic pain suggests that pain should be a key focus in RA management and should be assessed and addressed early and separately from the inflammatory component.Keywords: animal model, non-inflammatory, preclinical
format	article
author	Sebba A
author_facet	Sebba A
author_sort	Sebba A
title	Pain: A Review of Interleukin-6 and Its Roles in the Pain of Rheumatoid Arthritis
title_short	Pain: A Review of Interleukin-6 and Its Roles in the Pain of Rheumatoid Arthritis
title_full	Pain: A Review of Interleukin-6 and Its Roles in the Pain of Rheumatoid Arthritis
title_fullStr	Pain: A Review of Interleukin-6 and Its Roles in the Pain of Rheumatoid Arthritis
title_full_unstemmed	Pain: A Review of Interleukin-6 and Its Roles in the Pain of Rheumatoid Arthritis
title_sort	pain: a review of interleukin-6 and its roles in the pain of rheumatoid arthritis
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/cc0cb8149d6243feb3c59eb4d6cfdddf
work_keys_str_mv	AT sebbaa painareviewofinterleukin6anditsrolesinthepainofrheumatoidarthritis
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Pain: A Review of Interleukin-6 and Its Roles in the Pain of Rheumatoid Arthritis

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