MiR-216a-5p alleviates chronic constriction injury-induced neuropathic pain in rats by targeting KDM3A and inactivating Wnt/β-catenin signaling pathway.

Neuropathic pain is a devastating disease and exists tolerance to current available analgesics. MicroRNAs were reported to be involved in the regulation of neuropathic pain, but the biological role of miR-216a-5p in neuropathic pain remains unclear. In this study, we constructed a CCI rat model of neuropathic pain. Our results showed that the expression of miR-216a-5p was downregulated in CCI rats, and mechanical allodynia and thermal hyperalgesia in CCI rats were improved by miR-216a-5p overexpression, suggesting that miR-216a-5p overexpression alleviated neuropathic pain. Moreover, ELISA showed that miR-216a-5p overexpression inhibited concentration and mRNA expression of IL-6, TNF-α and IL-1β as well as suppressed microglial infiltration, indicating that miR-216a-5p overexpression inhibited neuroinflammation. Besides, we found that miR-216a-5p upregulation inactivated the Wnt/β-catenin signaling pathway. Furthermore, KDM3A was the downstream target of miR-216a-5p and KDM3A knockdown attenuated neuropathic pain. Finally, through rescue assay, we found that KDM3A countervailed miR-216a-5p mediated regulation of neuropathic pain via the Wnt/β-catenin signaling pathway. To sum up, our study confirmed that miR-216a-5p alleviated neuropathic pain in rats by targeting KDM3A and inactivating the Wnt/β-catenin signaling pathway, which may open a new and useful way for treatment of neuropathic pain.