Role of TNF-α/TNFR1 in intense acute swimming-induced delayed onset muscle soreness in mice

- Electronic von Frey test is useful to evaluate movement-induced muscle pain.
- Intense acute swimming can be used as a model of delayed onset muscle soreness.
- Targeting TNF-α/TNFR1 reduced DOMS as well as DOMS induces TNF-α production.
- TNF-α production occurs in the periphery (soleus muscle) and spinal cord.
- Targeting TNF-α/TNFR1 reduced inflammation, oxidative stress and pain.

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.