• Gastrocnemius injury model effectively mimics chronic muscle pain and inflammation. • Myositis animals exhibited reduced nociceptive thresholds and impaired locomotor activity. • Increased microglial activation in the lumbar spinal cord was associated with pain development. • Pharmacological inhibition of microglia improved nociceptive outcomes. • Cytokine profile revealed enhanced IL-4/IL-10 and reduced TNF-α and fractalkine, suggesting compensatory regulation. Musculoskeletal disorders are among the leading causes of disability worldwide, yet their underlying mechanisms remain incompletely understood. Experimental models of gastrocnemius muscle injury have been widely used to investigate the pathophysiology of chronic muscle pain. This study aimed to evaluate histological alterations in muscle tissue, nociceptive sensitivity, locomotor activity, and the role of spinal glial cells and inflammatory mediators following the induction of chronic myositis. Histological analyses revealed marked inflammation in the muscle tissue of myositis animals. Behavioral testing confirmed pain development, with reduced nociceptive thresholds compared to controls, as well as impaired locomotor activity. Increased expression of microglia in the lumbar spinal cord was also observed in myositis animals. Importantly, pharmacological inhibition of microglial activity using minocycline significantly improved nociceptive outcomes, reinforcing the potential of glial modulation in pain control. At the systemic level, cytokine analysis showed elevated levels of the anti-inflammatory cytokines IL-4 and IL-10, accompanied by reduced fractalkine and TNF-α levels in serum, suggesting activation of compensatory mechanisms that counterbalance the inflammatory process. Collectively, these findings advance our understanding of the cellular and molecular pathways involved in chronic muscle pain. By highlighting the contribution of glial cells and specific cytokines, our results support novel therapeutic approaches aimed at modulating neuroimmune interactions.
Freitas et al. (Sun,) studied this question.