Music alleviates pain perception in depression mouse models by promoting the release of glutamate in the hippocampus of mice to act on GRIK5

Objective: To explore the effect of music in pain perception and the molecular mechanism. Methods: Mice were separated to control, music, music + inhibitor, and saline group. Percentage pain reduction of mice in each group was determined. The contents of 5-HT, Glu, and NE in cerebrospinal fluid of mice in the four groups were determined by HPLC. FISH was used to analyze the distribution characteristics of GRIK5 in hippocampal tissues. The protein expressions of GRIK5, NMDA 1, and TRPC1 in the hippocampal tissues were determined via western blot. Results: Mice exposed to music showed a higher percentage of pain reduction compared to model animals, while injection of GRIK5 inhibitor weakened the effect of music. It increased the contents of 5-HT, Glu, and NE in mouse models of depression. The fluorescence signal in music group was significantly stronger than saline group. Music remarkably increased the expression of GRIK5, DLG4, NMDA 1, and TRPC1 proteins when compared with saline group. Conclusion: Music promoted the secretion of Glu. The glutaminergic pathway sensed Glu, subsequently activated GRIK5, DLG4, and NMDA 1 proteins to excite dopaminergic neurons, and finally promoted the production of 5-HT.