title: Role of TNF-α/TNFR1 in intense acute swimming-induced delayed onset muscle soreness in mice.
abstract: The injection of cytokines such as TNF-α induces muscle pain. Herein, it was addressed the role of endogenous TNF-α/TNFR1 signaling in intense acute swimming-induced muscle mechanical hyperalgesia in mice. Mice were exposed to water during 30 s (sham) or to a single session of 30-120 min of swimming. Intense acute swimming induced a dose-dependent (time of exercise-dependent) muscle mechanical hyperalgesia, which peaked after 24 h presenting characteristics of delayed onset muscle soreness (DOMS). The intense acute swimming (120 min)-induced muscle mechanical hyperalgesia was reduced in etanercept (soluble TNF receptor) treated and TNFR1 deficient ((-/-)) mice. TNF-α levels increased 2 and 4 h after intense acute swimming in soleus muscle (but not in gastrocnemius), and spinal cord, respectively. Exercise induced an increase of myeloperoxidase activity and decrease in reduced glutathione levels in an etanercept-sensitive and TNFR1-dependent manners in the soleus muscle, but not in the gastrocnemius muscle. Concluding, TNF-α/TNFR1 signaling mediates intense acute swimming-induced DOMS by an initial role in the soleus muscle followed by spinal cord, inducing muscle inflammatory hyperalgesia and oxidative stress. The knowledge of these mechanisms might contribute to improve the training of athletes, individuals with physical impairment and intense training such as military settings.
authors: Departamento de Patologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, CEP 86051-990, Cx Postal 6001, Londrina, Paraná, Brazil.
authors: Sergio M
authors: SM
authors: Borghi
authors: Departamento de Patologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, CEP 86051-990, Cx Postal 6001, Londrina, Paraná, Brazil.
authors: Ana C
authors: AC
authors: Zarpelon
authors: Departamento de Patologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, CEP 86051-990, Cx Postal 6001, Londrina, Paraná, Brazil.
authors: Felipe A
authors: FA
authors: Pinho-Ribeiro
authors: Departamento de Patologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, CEP 86051-990, Cx Postal 6001, Londrina, Paraná, Brazil.
authors: Renato D R
authors: RD
authors: Cardoso
authors: Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, CEP 86051-990, Londrina, Paraná, Brazil.
authors: Marli C
authors: MC
authors: Martins-Pinge
authors: Departamento de Patologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, CEP 86051-990, Cx Postal 6001, Londrina, Paraná, Brazil.
authors: Roberto I
authors: RI
authors: Tatakihara
authors: Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes, 3900, CEP 14049-900, Ribeirão Preto, São Paulo, Brazil.
authors: Thiago M
authors: TM
authors: Cunha
authors: Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes, 3900, CEP 14049-900, Ribeirão Preto, São Paulo, Brazil.
authors: Sergio H
authors: SH
authors: Ferreira
authors: Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes, 3900, CEP 14049-900, Ribeirão Preto, São Paulo, Brazil.
authors: Fernando Q
authors: FQ
authors: Cunha
authors: Departamento de Ciências Farmacêuticas, Centro de Ciências de Saúde, Hospital Universitário, Universidade Estadual de Londrina, Avenida Robert Koch, 60, CEP 86038-350, Londrina, Paraná, Brazil.
authors: Rubia
authors: R
authors: Casagrande
authors: Departamento de Patologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, CEP 86051-990, Cx Postal 6001, Londrina, Paraná, Brazil. Electronic address: waverri@uel.br.
authors: Waldiceu A
authors: WA
authors: Verri
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D000068800:Etanercept; D006854:Hydrocortisone / Q000097:blood; D006930:Hyperalgesia / Q000139:chemically induced; D007074:Immunoglobulin G / Q000494:pharmacology; D007962:Leukocytes / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000737:chemistry; D063806:Myalgia / Q000139:chemically induced / Q000209:etiology*; D009195:Peroxidase / Q000378:metabolism; D005082:Physical Exertion / Q000187:drug effects / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000502:physiology*; D013116:Spinal Cord / Q000737:chemistry; D013550:Swimming / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D000068800:Etanercept; D006854:Hydrocortisone
keywords: DOMS; Hyperalgesia; Muscle pain; Oxidative stress; Swimming; TNF-α