aO-conotoxin GeXIVA[1,2] reduced neuropathic pain and changed gene expression in chronic oxaliplatin-induced neuropathy mice model
Chemotherapy induced peripheral neuropathy (CIPN) is a dose-limiting painful neuropathy that occurs commonly during cancer management, which often leads to the discontinuation of medication. Previous studies suggest that the a9a10 nicotinic acetylcholine receptor (nAChR) specific antagonist aO-conotoxin GeXIVA[1,2] is effective in CIPN models, however the related mechanisms remains unclear. Here we analyzed the preventive effect of GeXIVA[1,2] on neuropathic pain in the long-term oxaliplatin injection induced CIPN model. At the end of treatment, lumbar (L4-L6) spinal cord was extracted, and RNA-sequencing and bioinformatic analysis were performed to investigate the potential genes and pathways related to CIPN and GeXIVA[1,2]. GeXIVA[1,2] inhibited the development of mechanical allodynia induced by chronic oxaliplatin treatment. Repeated injections of GeXIVA[1,2] for 3 weeks have no effect on mice normal pain threshold or locomotor activity and anxiety-like behavior as evaluated in the open field test (OFT) and elevated plus maze (EPM). Our RNA-sequencing results identified 209 differentially expressed genes (DEGs) in CIPN model, simultaneously injection of GeXIVA[1,2] with oxaliplatin altered 53 of the identified DEGs. These reverted genes were significantly enriched in immune-related pathways represented by cytokine-cytokine receptor interaction pathway. Our findings suggest that GeXIVA[1,2] could be a potential therapeutic compound for chronic oxaliplatin induced CIPN management. Overall design: We investigated the effect of chronic oxaliplatin and GeXIVA[1,2] treatment on mice L4-6 spinal cord gene expression. Four groups were divided into GS+NS control group, GS+GeXIVA group, OXL+NS group, and OXL+GeXIVA group for RNA-seq analysis. Each group has 3 biological replicates.