Skeletal muscle overuse injury: pathophysiological mechanisms, molecular pathways, and rehabilitation strategies

Skeletal muscle overuse injury (OUI) is a load-related condition that develops when repeated mechanical loading exceeds the adaptive and reparative capacity of skeletal muscle. Unlike acute traumatic injury or delayed-onset muscle soreness after unaccustomed eccentric exercise, chronic skeletal muscle OUI is characterized by recurrent subthreshold loading, insufficient recovery, persistent low-grade inflammation, impaired regeneration, and maladaptive remodeling. This narrative review summarizes and critically appraises current evidence on the conceptual boundaries, pathophysiological mechanisms, molecular pathways, and rehabilitation strategies of skeletal muscle OUI. Particular emphasis is placed on distinguishing direct skeletal muscle evidence from indirect or extrapolative evidence derived from acute injury models, adjacent musculoskeletal disorders, disease models, or preclinical studies. Key mechanisms include myofiber microdamage, satellite-cell-mediated repair, extracellular matrix remodeling, inflammatory signaling, oxidative stress, mitochondrial dysfunction, protein turnover, and myogenic transcriptional regulation. Current management remains centered on individualized load modification, graded rehabilitation, correction of biomechanical contributors, and criteria-based return to activity. Pharmacological and physical modalities may provide adjunctive symptom control in selected cases, whereas regenerative, gene-based, wearable-sensor-based, and artificial-intelligence-assisted approaches remain emerging or experimental for chronic skeletal muscle OUI. By integrating mechanistic evidence with rehabilitation practice and evidence appraisal, this review provides a focused framework for understanding, preventing, and managing skeletal muscle OUI.