Interactions Among Non-Coding RNAs and mRNAs in the Trigeminal Ganglion Associated with Neuropathic Pain

Abstract

Background Recent studies have demonstrated the contribution of non-coding RNAs (ncRNAs) to neuropathic pain. However, the expression profile of ncRNAs in the trigeminal ganglion (TG) and their functional mechanism underlying trigeminal neuropathic pain are still unclear. Methods In the present study, the trigeminal neuropathic pain model induced by chronic constriction injury of the infraorbital nerve (CCI-ION) was used to study the expression profile and potential regulatory mechanism of miRNAs, lncRNAs, circRNAs, and mRNAs in the TG by RNA-sequencing (RNA-seq) and bioinformatics analysis. CCI-ION mice suffered from mechanical allodynia from 3 days to 28 days after surgery. Results The RNA-seq results discovered 67 miRNAs, 216 lncRNAs, 14 circRNAs, 595 mRNAs, and 421 genes were differentially expressed (DE) in the TG of CCI-ION mice 7 days after surgery. And 39 DEGs were known pain genes. Besides, 5 and 35 pain-related DE mRNAs could be targeted by 6 DE miRNAs and 107 DE lncRNAs, respectively. And 23 pain-related DEGs had protein–protein interactions (PPI) with each other. GO analysis indicated membrane-related cell components and binding-related molecular functions were significantly enriched. KEGG analysis showed that nociception-related signaling pathways were significantly enriched for DE ncRNAs and DEGs. Finally, the competing endogenous RNA (ceRNA) regulatory network of DE lncRNA/DE circRNA-DE miRNA-DE mRNA existed in the TG of mice with trigeminal neuropathic pain. Conclusion Our findings demonstrate ncRNAs are involved in the development of trigeminal neuropathic pain, possibly through the ceRNA mechanism, which brings a new bright into the study of trigeminal neuropathic pain and the development of novel treatments targeting ncRNAs.

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

“…In another published study, a search aggregated a list of pain genes obtained from a series of pain databases as well as relevant literature sources for pain-related genes as well as their family genes ( Fang et al, 2022 ). We also analyzed the distribution of genes from the above pain gene list in cell clusters of the human and mouse TG and selected the output of genes with expression percentages greater than 5%, as shown in Supplementary Tables S1, S2 .…”

Post-Traumatic Trigeminal Neuropathy: Neurobiology and Pathophysiology

“…Recent studies have found missense mutations in both genes that encode the pore forming α1 subunit of the voltage-gated calcium channels, Cav3.1 and 3.2, resulting in gain of function and contributing to chronic pain [ 20 , 21 ]. Animal models of neuropathic pain involving chronic constriction injury of the infraorbital nerve have demonstrated that non-coding RNAs are involved in the development of trigeminal pain [ 6 , 22 ]. Following nerve injury, micro RNAs are downregulated in the dorsal root ganglion, which is thought to increase pain [ 23 ].…”

Emerging roles of miRNAs in neuropathic pain: From new findings to novel mechanisms

“…Numerous miRNAs are becoming more widely recognized as master switches in the pathophysiology condition and as regulators of various neuroinflammation and neuronal gene expression (Figure 2). Differential expression of various miRNAs has been directly reported in the dorsal root ganglion (DRG) after the induction of inflammatory and neuropathic pain (Fang et al, 2022). Therefore, it is necessary to discuss how miRNAs regulate the infiltration of immune cells and neuroinflammation after nerve injury.…”