Single-nucleus transcriptome analysis reveals transcriptional profiles of circadian clock and pain related genes in human and mouse trigeminal ganglion

INTRODUCTION: Clinical studies have revealed the existence of circadian rhythms in pain intensity and treatment response for chronic pain, including orofacial pain. The circadian clock genes in the peripheral ganglia are involved in pain information transmission by modulating the synthesis of pain mediators. However, the expression and distribution of clock genes and pain-related genes in different cell types within the trigeminal ganglion, the primary station of orofacial sensory transmission, are not yet fully understood. METHODS: In this study, data from the normal trigeminal ganglion in the Gene Expression Omnibus (GEO) database were used to identify cell types and neuron subtypes within the human and mouse trigeminal ganglion by single nucleus RNA sequencing analysis. In the subsequent analyses, the distribution of the core clock genes, pain-related genes, and melatonin and opioid-related genes was assessed in various cell clusters and neuron subtypes within the human and mouse trigeminal ganglion. Furthermore, the statistical analysis was used to compare the differences in the expression of pain-related genes in the neuron subtypes of trigeminal ganglion. RESULTS: The present study provides comprehensive transcriptional profiles of core clock genes, pain-related genes, melatonin-related genes, and opioid-related genes in different cell types and neuron subtypes within the mouse and human trigeminal ganglion. A comparative analysis of the distribution and expression of the aforementioned genes was conducted between human and mouse trigeminal ganglion to investigate species differences. DISCUSSION: Overall, the results of this study serve as a primary and valuable resource for exploring the molecular mechanisms underlying oral facial pain and pain rhythms.