The stress-fascia-pain axis in myofascial pain syndrome: a mechanistic integrative review and conceptual synthesis.

Background: Myofascial pain syndrome (MPS) is common in musculoskeletal practice, but its persistence, recurrence, and clinical heterogeneity are not fully explained by a muscle-only model. The integrated hypothesis remains central to understanding the active trigger point itself, yet patients with longstanding symptoms often show a broader picture, including stress-related fluctuation, disturbed sleep, regional spread, autonomic imbalance, and only partial benefit from strictly local treatment. Objective: To examine whether trigger-point biochemistry, fascial dysfunction, stress-related neuroendocrine change, autonomic imbalance, and altered pain processing can be brought together within a single account of persistence and recurrence in MPS. Methods: We conducted a mechanistic integrative review using PRISMA 2020 reporting principles. MEDLINE/PubMed, Scopus, Web of Science Core Collection, and the Cochrane Library were searched from inception to 28 February 2026. The review question was framed using a modified PICOS structure. Because the literature comprised heterogeneous human, translational, and animal studies and was not suitable for pooled quantitative analysis, findings were synthesized narratively, with reporting informed by SWiM principles. Study screening, data extraction, and methodological appraisal were performed by a single reviewer; the review protocol was prespecified but was not prospectively registered. The included studies were grouped into four mechanistic domains: trigger-point microenvironment, fascial biomechanics and tissue gliding, stress-related endocrine-immune and autonomic dysregulation, and central amplification. Results: The search identified 1,246 records; 318 duplicates were removed, 928 titles and abstracts were screened, and 121 full texts were assessed for eligibility. Fifty-seven studies were included in the qualitative synthesis. Across domains, the literature supports a multilevel account in which the active trigger point constitutes the peripheral nociceptive core; fascial innervation, myofibroblast activity, and impaired hyaluronan-mediated gliding may contribute to local stiffness and persistence; stress-related autonomic and hypothalamic-pituitary-adrenal dysregulation may hinder recovery; and persistent nociceptive input may facilitate central amplification in susceptible phenotypes. Evidence is strongest for local biochemical sensitization and more indirect, though broadly convergent, for sympathetic-fascial and neuroendocrine mechanisms. Conclusion: Taken together, the available evidence supports a conceptual Stress-Fascia-Pain axis that may help explain recurrence, heterogeneity, and variable treatment response in MPS. This heuristic framework does not displace established trigger-point models; rather, it situates them within a broader integrative account that links local nociception with tissue biomechanics, stress physiology, and pain-system plasticity. Evidence strength varies across domains: it is most direct for trigger-point biochemistry and more indirect or hypothesis-generating for sympathetic-fascial remodeling and endocrine-immune persistence. The framework also supports a multimodal, phenotype-sensitive clinical approach in which local treatment is combined, when indicated, with graded movement, stress regulation, autonomic recovery, sleep restoration, and pain-modulating strategies. Validation through prospective longitudinal and multimodal studies remains a priority. Registration: The review protocol was specified before screening and data extraction but was not prospectively registered in a public repository.