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.