Author:
Borghi Sergio M.,Bussulo Sylvia K. D.,Pinho-Ribeiro Felipe A.,Fattori Victor,Carvalho Thacyana T.,Rasquel-Oliveira Fernanda S.,Zaninelli Tiago H.,Ferraz Camila R.,Casella Antônio M. B.,Cunha Fernando Q.,Cunha Thiago M.,Casagrande Rubia,Verri Waldiceu A.
Abstract
Unaccustomed exercise involving eccentric contractions, high intensity, or long duration are recognized to induce delayed-onset muscle soreness (DOMS). Myocyte damage and inflammation in affected peripheral tissues contribute to sensitize muscle nociceptors leading to muscle pain. However, despite the essential role of the spinal cord in the regulation of pain, spinal cord neuroinflammatory mechanisms in intense swimming-induced DOMS remain to be investigated. We hypothesized that spinal cord neuroinflammation contributes to DOMS. C57BL/6 mice swam for 2 h to induce DOMS, and nociceptive spinal cord mechanisms were evaluated. DOMS triggered the activation of astrocytes and microglia in the spinal cord 24 h after exercise compared to the sham group. DOMS and DOMS-induced spinal cord nuclear factor κB (NFκB) activation were reduced by intrathecal treatments with glial inhibitors (fluorocitrate, α-aminoadipate, and minocycline) and NFκB inhibitor [pyrrolidine dithiocarbamate (PDTC)]. Moreover, DOMS was also reduced by intrathecal treatments targeting C-X3-C motif chemokine ligand 1 (CX3CL1), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β or with recombinant IL-10. In agreement, DOMS induced the mRNA and protein expressions of CX3CR1, TNF-α, IL-1β, IL-10, c-Fos, and oxidative stress in the spinal cord. All these immune and cellular alterations triggered by DOMS were amenable by intrathecal treatments with glial and NFκB inhibitors. These results support a role for spinal cord glial cells, via NFκB, cytokines/chemokines, and oxidative stress, in DOMS. Thus, unveiling neuroinflammatory mechanisms by which unaccustomed exercise induces central sensitization and consequently DOMS.
Funder
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Fundação Nacional de Desenvolvimento Do Ensino Superior Particular
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Subject
Pharmacology (medical),Pharmacology
Cited by
8 articles.
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