Study of alternative splicing events associated with hyperalgesia

Abstract

Prolonged use of opioids could cause oversensitivity to stimuli and opioid-induced hyperalgesia (OIH). Despite reports of differential gene expression associated with OIH and known alternative splicing of these differentially expressed genes, the impact of alternative splicing on OIH remains partially characterized. Alternative splicing mechanisms were studied to gain a comprehensive understanding of the effects of alternative splicing on OIH elicited by chronic morphine exposure. The characterization of alternative splicing in the trigeminal ganglia and nucleus accumbens of mice enabled the identification of region-dependent splicing mechanisms underlying OIH. Genes that participate in glutamatergic synapse and myelin protein processes presented splicing mechanism associated with OIH. A prevalence of alternative splicing events associated with OIH was identify in the platelet derived growth factor, axon guidance, and integrin signaling pathways. A notable finding was the prevalence of alternatively spliced transcription factors and enriched transcriptional regulators. Our study offered insights into the nociceptive and antinociceptive modulatory action of alternatively spliced genes. The results from our study highlight the impact of alternative splicing mechanisms and transcriptional regulators associated with OIH. These findings enhance the accuracy of OIH therapeutic target studies.