Inflammatory Biochemical Mediators and Their Role in Myofascial Pain and Osteopathic Manipulative Treatment: A Literature Review

Myofascial pain (MFP) is one of the leading reasons for medical visits related to chronic pain, characterized by the presence of muscular trigger points that produce pain on palpation and muscular dysfunction. This literature review investigated the biochemical mechanisms underlying MFP, with a particular focus on inflammatory mediators and the role of osteopathic manipulative treatment (OMT). The research analyzed 17 scientific articles to elucidate the molecular pathways involved in the pathogenesis and treatment of MFP. Myofascial tissue is a continuous layer of connective tissue that provides muscular stabilization and connection, composed mainly of a dense network of collagen and elastin.

Fibroblasts are the predominant cells in this tissue and play a fundamental role in the processes of injury and tissue repair. The pathophysiology of MFP is based on the dual-innervation theory at the neuromuscular endplate, in which dysfunctions in this system lead to release of inflammatory mediators that stimulate nociceptive pathways. The main inflammatory mediators identified in MFP include interleukin-1β (IL-1β), IL-6, IL-8, tumor necrosis factor-α (TNF-α), substance P, bradykinin, and norepinephrine. TNF-α, in particular, plays a unique role by activating a proinflammatory cascade through binding to the TNFR1 receptor, culminating in activation of nuclear factor κB (NF-κB).

The cells involved in the inflammatory process include fibroblasts, satellite cells, and macrophages, each contributing in specific ways to tissue repair and perpetuation of the inflammatory response. Studies have demonstrated significantly elevated concentrations of proinflammatory mediators in patients with MFP, including reduced pH and increased bradykinin, substance P, TNF-α, IL-1β, IL-6, IL-8, serotonin, and norepinephrine, both at active trigger-point sites and at remote sites, confirming a systemic manifestation of inflammation. Treatment of MFP traditionally includes pharmacologic options such as nonsteroidal anti-inflammatory drugs (NSAIDs), benzodiazepines, and tricyclic antidepressants, but these approaches frequently have a significant adverse-effect profile and limited efficacy. By contrast, nonpharmacologic modalities — particularly OMT — demonstrate therapeutic efficacy with a more favorable side-effect profile.

Specific OMT techniques have shown measurable molecular effects: static stretching increased the cross-sectional area of fibroblast bodies, correlating with localized decreases in tissue tension. Myofascial release demonstrated the ability to accelerate healing, stimulate muscle regeneration, and reduce inflammation through modulation of fibroblast activity. Indirect techniques such as counterstrain reduced IL-6 levels, while dry needling decreased substance P and increased endogenous β-endorphin. Low-level laser therapy showed significant reductions in TNF-α and substance P in animal models.

These findings suggest that OMT modalities exert therapeutic effects through specific molecular mechanisms, modulating the inflammatory response and promoting tissue repair. Myofascial release, in particular, demonstrates the ability to facilitate fibroblast-mediated myoblast differentiation and improve healing of repetitive strain muscle injuries. The clinical implications of these findings are substantial, suggesting that nonpharmacologic approaches may offer effective and safer alternatives for the management of MFP. Understanding the molecular mechanisms underlying OMT may inform the development of more precise and personalized therapeutic protocols.

The study identifies the need for future research to fully elucidate the mechanisms by which different OMT techniques modulate specific inflammatory markers. While the results are promising, limitations include heterogeneity of the studies reviewed, variability in the OMT techniques analyzed, and the need for additional controlled clinical trials. A multifactorial approach remains the optimal strategy for managing MFP, integrating pharmacologic and nonpharmacologic modalities based on understanding of the underlying pathophysiologic mechanisms.