Mechanosensitive Ion Channels and Neuroplasticity in Tuina Therapy: Molecular Mechanisms and Therapeutic Implications

Tuina is a traditional Chinese manual therapy distinguished from generic massage by its acupoint- and meridian-based manipulations, and it is commonly used in the management of neurological and musculoskeletal disorders, although its underlying biological mechanisms remain incompletely defined. This review summarizes current experimental and clinical evidence on the neurobiological processes associated with Tuina therapy, with a focus on pain modulation and neural repair. Available evidence suggests that mechanical stimulation during Tuina may engage mechanosensitive ion channels, including transient receptor-potential vanilloid (TRPV)1, transient receptor-potential ankyrin 1 (TRPA1), and Piezo channels, thereby modulating nociceptive signaling, nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) and toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB)-related inflammatory pathways, Piezo1/Piezo2- and YAP/TAZ-associated mechanotransduction, neurotransmitters and neuropeptides, and descending pain inhibitory circuits involving the periaqueductal gray (PAG)-rostral ventromedial medulla (RVM) system. In addition, emerging evidence indicates that Tuina may affect peripheral and central neuroplastic processes, including modulation of neuronal excitability, glial activity, and functional brain networks. While these findings provide a mechanistic framework for understanding reported clinical effects in conditions such as neuropathic pain (NP), low back pain (LBP), cervical disorders, and headache, heterogeneity in study design and intervention protocols limits definitive conclusions. Further well-designed mechanistic studies and standardized clinical trials are required to clarify the role of Tuina in pain regulation and neuroplasticity and to support its evidence-based application in clinical practice.