A mechanistic hypothesis: osteopathic manipulative therapy may modulate immune cell function in chronic low back pain

Chronic low back pain (CLBP) remains a leading cause of disability worldwide and is increasingly recognized as a condition that involves immune-mediated neuroinflammatory mechanisms. Osteopathic manipulative therapy (OMT) is a widely used non-invasive, non-pharmacological treatment for chronic pain; however, the molecular mechanisms underlying OMT effectiveness are not fully understood. We propose a mechanistic hypothesis of how OMT may influence circulating immune-cell gene expression and immune-cell distribution, with downstream effects on inflammatory signaling and neuroimmune sensitization. The mechanical forces applied during OMT could affect immune cell function, including leukocyte trafficking and cytokine activity. These mechanical influences may alter transcriptional activity within peripheral blood mononuclear cells, and over time, contribute to changes in gene expression patterns. This hypothesis article synthesizes current evidence from immunology, mechanobiology, and osteopathic clinical research to outline a proposed transcriptomic framework linking OMT to neuroimmune regulation in CLBP. This hypothesis supports a possible role for OMT in chronic pain management and suggests that immune modulation may represent one potential mechanism contributing to therapeutic benefit in persistent pain conditions. While current evidence suggests that OMT may influence immune function, direct transcriptomic validation remains limited and warrants further investigation through larger mechanistic studies.