Tuina ameliorates sleep disturbances in PCPA-treated rats through Piezo1-mediated calcium signaling.

OBJECTIVES: Insomnia is a prevalent sleep disorder that severely impairs physical and mental health. Clinical research has shown that Tuina, a form of therapeutic massage, can improve sleep quality and restore normal sleep patterns, yet the underlying biological mechanism remains unclear. This study aimed to determine whether Tuina improves sleep-related behaviors by modulating the Piezo1-calcium signaling pathway through mechanical stimulation of the nervous system. MATERIALS AND METHODS: A rat model of sleep disturbances was induced using PCPA. Rats received daily Tuina on the dorsal regions corresponding to the Governor Vessel and Bladder meridians. sleep-related behavioral parameters, cognitive function, hippocampal neurotransmitters, and expression of Piezo1 and downstream proteins (CaM, CaN) were assessed. The Piezo1 agonist Yoda1 was used to verify mechanistic involvement. RESULTS: Tuina treatment significantly improved sleep-related behavioral parameters and cognitive performance in PCPA-treated rats. At the molecular level, PCPA-induced sleep disruption led to Piezo1 upregulation, intracellular calcium overload, and subsequent overactivation of the CaM/CaN signaling pathway. These alterations were accompanied by neurotransmitter imbalance and hippocampal neuronal damage. Tuina intervention effectively suppressed Piezo1 expression, normalized calcium homeostasis, and inhibited downstream CaM/CaN activation, thereby restoring neurotransmitter levels and preserving neuronal integrity. Critically, the therapeutic benefits of Tuina were largely reversed by co-administration of the Piezo1 agonist Yoda1, supporting the involvement of Piezo1-mediated calcium signaling in its mechanism of action. CONCLUSION: Tuina's therapeutic effect involves suppression of Piezo1-dependent calcium signaling, contributing to normalization of hippocampal function and neurotransmitter balance. This provides mechanistic evidence that Tuina's mechanical stimulation modulates sleep-related behavioral endpoints via central mechanosensitive ion channels.