Effect of Rimegepant treatment on gene expression in the trigeminal ganglion of mice on the tumor-transplanted side.

The trigeminal nerve is primarily responsible for facial sensation and exhibits the highest expression of CGRP. Here, we explored the impact of Rimegepant on the transcriptome of the trigeminal ganglion in mice and found that the transcription profiles changed significantly following treatment compared to the control group. Following Rimegepant administration, we observed a significant downregulation of innate immune-related items within the trigeminal ganglia, as well as functional items directly associated with pain perception and calcium signaling pathways.The activation of innated immune within the trigeminal ganglia is known to enhance nociceptive responses, which were also directly linked to the activation of calcium signaling pathways. These results suggest that Rimegepant alleviates OSCC-related pain by mitigating the inflammatory condition within the trigeminal ganglion. We then categorized the genes enriched in these functional groups. Genes that promote the proliferation and differentiation of innate immune cells, and those related to the expression of proinflammatory mediators, were significantly downregulated, while those associated with anti-inflammatory functions were significantly upregulated. Additionally, genes from various chemokine receptor families and ion channel genes linked to neuronal activity were significantly downregulated. Collectively, these results suggest that CGRP influences OSCC-related pain by modulating the innate immune status of the trigeminal nerve. Overall design: To investigate the mechanism of Rimegepant on OSCC-related pain, we established unilateral tongue orthotopic transplantation modelson BALB/c nude mice which were randomly divided into an experimental group and a control group (n=3 in each group). In the experimental group, Rimegepant was intraperitoneally injected every 24 h for 4 consecutive days, starting from the 5th day after tumor inoculation. The control group received an equal volume of physiological saline. After the final drug treatment, both groups of mice were euthanized, with the trigeminal ganglia on the side of the transplantation tumor carefully isolated.