Inhibition of lncRNA X inactivate-specific transcript ameliorates inflammatory pain by suppressing satellite glial cell activation and inflammation by acting as a sponge of miR-146a to inhibit Nav 1.7.

Abstract

Long noncoding RNAs (lncRNA) has been validated to participate in nociception in inflammatory pain, presenting as a potential target against anesthesia. Previous research work confirmed the correlation between lncRNA X inactivate-specific transcript (XIST) and inflammation. However, its role in inflammatory pain is undefined. In animal pain models, voltage-gated sodium channels (VGSCs) reportedly participate in neural excitation. In this study, we observed the high expression of XIST and VGSC 1.7 (Nav 1.7) in the dorsal root ganglion (DRG) of the complete Freund's adjuvant (CFA)-induced rat inflammatory pain model. Furthermore, XIST inhibition alleviated pain behavior and the activation of DRG satellite glial cells by suppressing glial fibrillary acidic protein (GFAP) expression, as well as inflammatory cytokine levels of interleukin-6 and tumor necrosis factor-α. XIST downregulation increased the mechanical pain threshold in an inflammatory pain model. Moreover, the expression of miR-146a was decreased in CFA rats. In vitro, XIST acted as a sponge of miR-146a, which targeted Nav 1.7 via bioinformatic prediction, luciferase reporter, and pull-down assay. More importantly, activation of the Nav 1.7 pathway or miR-146 depression both reversed XIST knockdown-inhibited satellite glial cell activation and inflammatory pain in CFA rats. These results suggest that cessation of XIST may ameliorate inflammatory pain by acting as a sponge of miR-146a to inhibit Nav1.7, implying a promising strategy against inflammatory pain.