Dorsal root ganglia coactivator-associated arginine methyltransferase 1 contributes to peripheral nerve injury-induced pain hypersensitivities.

Aims: Neuropathic pain is associated with gene expression changes within the dorsal root ganglia (DRG), which are involved in epigenetic mechanisms. However, whether protein arginine methylation plays an epigenetic role is unknown. In this study, we aimed to determine how peripheral nerve injury changes the transcriptional expression of the protein arginine methylation enzyme family genes in injured DRG and further to investigate their roles in neuropathic pain after nerve injury. Methods: RNA-Seq was used to comprehensively analyze changes in the protein expression of arginine methyltransferases and its demethylase in the injured DRG neuronal system following spinal nerve ligation (SNL) and to screen differentially expressed genes in injured DRGs following SNL. After qPCR verification of these differentially expressed genes at corresponding timepoints after SNL and sciatic nerve chronic constriction injury (CCI), CCI-induced arginine methyltransferase coactivator-associated arginine methyltransferase 1 (CARM1) increases were blocked by microinjection of its corresponding siRNA in injured DRG, and observations were made to determine whether it attenuated the behaviors of CCI-induced pain hypersensitivities. Key findings: Peripheral nerve injury induced the upregulation of the protein expression of CARM1 in the injured DRG and blocking its expression in the injured DRG attenuated the development and maintenance of neuropathic pain after peripheral nerve injury. Significance: Given that CARM1 siRNA attenuated the development and maintenance of neuropathic pain after peripheral nerve injury, our findings suggest that CARM1 in clinical applications may be a good target for neuropathic pain treatment.