MyofascialPainSyndrome:AnUnderstandingofMolecularBiologyandManagement

Myofascial pain syndrome (MPS) is one of the most common causes of musculoskeletal pain, yet its underlying mechanisms remain incompletely understood. The condition is characterized by the presence of trigger points—hyperirritable nodules within taut bands of skeletal muscle that produce local and referred pain. MPS significantly impacts quality of life, work productivity, and healthcare utilization. Despite its prevalence, there has been ongoing debate about whether MPS represents a primarily peripheral muscle disorder or involves central nervous system sensitization.

Understanding the molecular and cellular mechanisms behind MPS is essential for developing more targeted and effective treatments beyond traditional symptomatic approaches.

This narrative review synthesizes current knowledge on the molecular biology of myofascial pain syndrome and its clinical management. The authors examined the pathophysiological mechanisms underlying trigger point formation and persistence, including local muscle changes, neurogenic inflammation, and central sensitization processes. They reviewed evidence on the biochemical environment within active trigger points, including alterations in pH, inflammatory mediators, and neuropeptides. The review also evaluated current diagnostic approaches and treatment modalities, assessing their mechanistic rationale and evidence base.

The review identifies several key molecular mechanisms in MPS pathophysiology. Within trigger points, there is evidence of sustained sarcomere shortening leading to local ischemia and hypoxia, creating an acidic environment with lowered pH. This acidic milieu activates nociceptors and promotes release of inflammatory mediators including substance P, calcitonin gene-related peptide (CGRP), bradykinin, serotonin, and prostaglandins. These substances sensitize peripheral nociceptors and contribute to local and referred pain patterns.

The authors highlight that prolonged nociceptive input from trigger points can induce neuroplastic changes in the spinal cord and brain, leading to central sensitization—where pain processing becomes amplified and pain may persist even after peripheral input diminishes. The review also discusses the role of autonomic dysfunction in MPS, with evidence of altered sympathetic activity influencing trigger point pathophysiology. Regarding management, the authors note that while various treatments exist—including manual therapy, dry needling, trigger point injections, and physical modalities—the evidence base varies considerably, and multimodal approaches addressing both peripheral and central mechanisms appear most promising.

For clinicians, this review emphasizes that MPS should be understood as a condition involving both peripheral tissue changes and central nervous system plasticity. This dual mechanism has important treatment implications: effective management may require combining peripheral interventions (such as trigger point release or dry needling) with approaches that address central sensitization (including graded exercise, pain education, and cognitive-behavioral strategies). The molecular understanding of trigger points supports the use of interventions that improve local tissue perfusion, reduce inflammatory mediator accumulation, and normalize muscle spindle activity. For patients, this research validates that myofascial pain has real biological underpinnings and is not merely psychosomatic.

It also suggests that persistent or recurrent MPS may indicate ongoing central sensitization, requiring more comprehensive rehabilitation approaches rather than repeated local treatments alone. Future research directions include developing biomarkers for MPS, creating more targeted pharmacological interventions based on specific molecular pathways, and better defining which patient subgroups respond best to particular treatment combinations.