Regular swimming exercise prevented the acute and persistent mechanical muscle hyperalgesia by modulation of macrophages phenotypes and inflammatory cytokines via PPAR gamma receptors

Physically active individuals are less likely to develop chronic pain, and physical exercise is an established strategy to control inflammatory diseases. Here, we hypothesized that 1) peripheral pro-inflammatory macrophages phenotype contribute to predisposition of the musculoskeletal to chronic pain, and that 2) activation of PPAR gamma receptors, modulation of macrophage phenotypes and cytokines through physical exercise would prevent persistent muscle pain. We tested these hypotheses using swimming exercise, pharmacological and immunochemical techniques in a rodent model of persistent muscle hyperalgesia. Swimming prevented the persistent mechanical muscle hyperalgesia most likely through activation of PPAR gamma receptors, as well as activation of PPAR gamma receptors by 15d-PGJ2 and depletion of muscle macrophages in sedentary animals. Acute and persistent muscle hyperalgesia were characterized by an increase in pro-inflammatory macrophages phenotype, and swimming and the 15d-PGJ2 prevented this increase and increased anti-inflammatory macrophages phenotype. Finally, IL-1 beta concentration in muscle increased in the acute phase, which was also prevented by PPAR gamma receptors activation through swimming. Besides, swimming increased muscle concentration of IL-10 in both acute and chronic phases, but only in the persistent phase through PPAR gamma receptors. Our findings suggest physical exercise activates PPAR gamma receptors and increases anti-inflammatory responses in the muscle tissue by modulating macrophages phenotypes and cytokines, thereby preventing the establishment of persistent muscle hyperalgesia. These results further highlight the potential of physical exercise to prevent chronic muscle pain. (AU)