Acupuncture-Mediated Neuro-Immune Regulation in Musculoskeletal Pain: Mechanisms and Therapeutic Perspectives

Musculoskeletal disorders (MSDs) are a major cause of chronic pain and disability worldwide, and are increasingly recognized as conditions driven by persistent inflammation and impaired tissue repair. Acupuncture has been widely used for the management of MSDs, yet its underlying mechanisms are often described in isolation at different biological levels. In this narrative review, we synthesize current evidence on how acupuncture regulates inflammatory responses in MSDs, with a particular focus on neuro-immune interactions and downstream effects on tissue repair. Accumulating studies show that acupuncture can suppress pro-inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), while enhancing anti-inflammatory signals including interleukin-10 (IL-10). It also influences immune cell behavior, especially macrophage polarization, and modulates key signaling pathways such as Toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB), NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, and mitogen-activated protein kinase (MAPK) cascades. Beyond inflammation control, these regulatory effects are closely linked to the activation of repair-related cells, including mesenchymal stem cells, fibroblasts, and osteoblasts. Taken together, current evidence suggests that the therapeutic effects of acupuncture arise from coordinated interactions among neural signaling, immune regulation, and tissue repair processes, forming an integrated neuro-immune-repair network. Although the overarching conceptual framework is relatively clear, much of the supporting evidence derives from preclinical models, indirect observations, or inferences extrapolated from non-musculoskeletal systems. Therefore, this review explicitly distinguishes direct musculoskeletal evidence from broader mechanistic extrapolations, while highlighting substantial heterogeneity across existing studies and the ongoing need for robust clinical validation. Overall, this systems-level framework offers a conceptual diagrammatic architecture for hypothesis generation, serving as a heuristic guide rather than a fully validated predictive model for understanding acupuncture in musculoskeletal disorders.