Decoding the fibroblast/mast cell signaling pathway of acupuncture

Acupuncture has been practiced for thousands of years with documented therapeutic effects, yet its underlying biological mechanisms remain poorly understood. Here, we show that acupuncture stimulation converts local mechanical forces into neuronal signals through defined cellular interactions, establishing a causal axis that links micro-level events at the ST36 acupoint to systemic therapeutic effects. We demonstrate that acupuncture needle manipulation transmits mechanical tension through collagen fibers to local fibroblasts, which subsequently secrete stem cell factor (SCF) and interleukin-33 (IL-33) in the acupoint. SCF recruits mast cells, while IL-33 induces their activation and the release of neuromodulatory molecules. These molecules then engage the nervous system, as evidenced by c-fos expression in the lumbar dorsal horn, demonstrating the transmission of acupuncture-induced peripheral signals into central circuits. Together, these findings define a functional axis linking needle-evoked stimulation to neuronal activation and provide a mechanistic framework for understanding the biological basis of acupuncture and for its evidence-based refinement.