Role of integrin αvβ5 receptor and microglia in delayed-onset muscle soreness in mice

Delayed-onset muscle soreness (DOMS) is characterized by muscle pain, stiffness, and tenderness following intense or unaccustomed exercise. In humans, symptoms typically arise 6-72 h post-exercise. This study investigated a novel mechanism underlying DOMS, focusing on the involvement of the irisin receptor integrin αvβ5 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 αvβ5 was evaluated via intrathecal administration of the antagonist cilengitide, given both prior to exercise and 24 h post-exercise. To assess irisin's 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 αvβ5 and spinal microglia play critical roles in DOMS pathogenesis, with irisin and pro-inflammatory cytokines as key mediators.