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Although historically attributed to joint inflammation, recent evidence reveals a multifactorial pathogenesis of RA pain, involving peripheral sensitization, central sensitization, and neuroimmune crosstalk. In these mechanisms, interleukin\u20106 (IL\u20106) plays a central role not only as one of the inflammatory mediators but also as a classic and trans\u2010signaling modulator for pain. This review synthesizes current mechanistic and clinical evidence on IL\u20106 inhibitors, particularly sarilumab and tocilizumab, concerning their effect on pain in RA. Preclinical studies have already demonstrated that IL\u20106 enhances the excitability of nociceptors through the upregulation of ion channels in dorsal root ganglia; it also promotes glial activation within the spinal cord; however, chronic pain sustains these processes. Blockade of IL\u20106 receptor reverses these changes and alleviates mechanical hyperalgesia as well as allodynia in different models of diseases. Clinical trials of IL\u20106 inhibitors have shown that these compounds provide major pain relief, sometimes better than tumor necrosis factor (TNF) inhibitors, most explicitly for patients with elevated baseline C\u2010reactive protein (CRP) or who do not respond to TNF inhibitors. Differences in their pharmacokinetics, receptor binding, and suppression of CRP may translate into differences in their analgesic profiles. However, it is analyzed that a subset of patients with persistently painful rheumatoid arthritis despite IL\u20106 inhibition demonstrates the existence of non\u2010inflammatory drivers like nociplastic pain and the inadequacy of conventional indices of disease activity to capture the burden of pain.<\/jats:p>","DOI":"10.1002\/prp2.70219","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T08:43:01Z","timestamp":1774514581000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effect of Interleukin\u20106 Inhibitors on Rheumatoid Arthritis Pain: Overview of Evidence and Mechanistic Pathways"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7848-6600","authenticated-orcid":false,"given":"Andrej","family":"Belan\u010di\u0107","sequence":"first","affiliation":[{"name":"Department of Basic and Clinical Pharmacology and Toxicology Faculty of Medicine, 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