RNA-seq analysis of ipsilateral rat TGs on day 14 after CCI-ION or sham operation

Nerve injury-induced changes in gene expression in primary sensory neurons, such as trigeminal ganglion (TG) neurons, play a critical role in the genesis of neuropathic pain. Therefore, understanding the molecular mechanisms underlying these changes in the TGs following peripheral nerve injury will enable us to develop a new avenue for managing trigeminal-mediated neuropathic pain. Studies have highlighted the involvement of miRNA-mediated modulation in a wide range of diseases, leading to the exploration of miRNA-based therapeutics as a potential treatment strategy. Here, in this RNA-seq database, we have found that microRNA-216a-3p (miR-216a-3p) and miR-32-5p (miR-32-5p), which are downregulated in injured TGs, are novel functional RNAs involved in regulating trigeminal-mediated neuropathic pain. Histone methylation-mediated miRNA downregulation in TG neurons regulates trigeminal neuropathic pain by targeting either STIM1 (H3K27me3/SOX10/miR-216a-3p/STIM1) or Cav3.2 (GR/miR-32-5p/Cav3.2) channels. Moreover, we found that miR-323-3p exhibited the most significant upregulation in the injured TG. Understanding the mechanistic role of the PRMT2/FOXA2/miR-323-3p/Kv2.1 signaling axis in sensory neurons may advance the discovery of novel therapeutic strategies for neuropathic pain.