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In humans, symptoms typically arise 6\u201372\u00a0h post-exercise. This study investigated a novel mechanism underlying DOMS, focusing on the involvement of the irisin receptor integrin \u03b1v\u03b25 and spinal microglia in its development. Male C57BL\/6 mice were subjected to a DOMS model induced by an acute aerobic exercise protocol, and nociceptive thresholds were assessed using the von Frey filament test. The role of spinal integrin \u03b1v\u03b25 was evaluated via intrathecal administration of the antagonist cilengitide, given both prior to exercise and 24\u00a0h post-exercise. To assess irisin\u2019s nociceptive effects, it was also administered intrathecally. Additionally, minocycline, a microglial inhibitor, was administered before irisin to determine microglial involvement. An in vitro assay evaluated microglial activation by irisin via flow cytometry. Pro- and anti-inflammatory cytokines were quantified by ELISA. Cilengitide reversed exercise-induced DOMS and reduced spinal pro-inflammatory cytokines. Irisin induced nociception, which was attenuated by minocycline. Irisin also activated microglia in vitro, increasing pro-inflammatory cytokine production. These findings suggest integrin \u03b1v\u03b25 and spinal microglia play critical roles in DOMS pathogenesis, with irisin and pro-inflammatory cytokines as key mediators.<\/jats:p>","DOI":"10.1007\/s10974-026-09742-1","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:55:54Z","timestamp":1792727754000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of integrin \u03b1v\u03b25 receptor and microglia in delayed-onset muscle soreness in mice"],"prefix":"10.1007","volume":"47","author":[{"given":"Bruno Lopes Gon\u00e7alves","family":"Rocha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio Protasio","family":"Veras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaela Silva","family":"dos Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alben\u00e1","family":"Nunes-Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago Roberto Lima","family":"Romero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovane","family":"Galdino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,23]]},"reference":[{"key":"9742_CR1","doi-asserted-by":"publisher","first-page":"1903","DOI":"10.1016\/j.molcel.2023.05.008","volume":"83","author":"M A","year":"2023","unstructured":"A M, Wales TE, Zhou H et al (2023) Irisin acts through its integrin receptor in a two-step process involving extracellular Hsp90\u03b1. 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