MiR-216b-5p attenuates chronic constriction injury-induced neuropathic pain in female rats by targeting MAL2 and inactivating Wnt/β-catenin signaling pathway.

MicroRNAs (miRNAs) are crucial regulators of neuronal functions and participate in the development of neuropathic pain. MiR-216b-5p has been reported to be involved in the progression of many human diseases. However, the biological effect and regulatory mechanism of miR-216b-5p in neuropathic pain have not been found. In this study, we aimed to explore the function of miR-216b-5p in neuropathic pain through constructing rat models with neuropathic pain by chronic constriction injury (CCI) method. MiR-216b-5p was found to be downregulated in CCI rat models, suggesting that miR-216b-5p played a role in neuropathic pain. Next, it was proved that miR-216b-5p overexpression attenuated neuropathic pain and neuroinflammation in CCI rats. In addition, miR-216b-5p overexpression was found to inhibit Wnt/β-catenin signaling pathway, and myelin and lymphocyte protein 2 (MAL2) was the downstream target of miR-216b-5p. MiR-216b-5p inactivated the Wnt/β-catenin signaling pathway through downregulation of MAL2. Moreover, MAL2 knockdown was confirmed to alleviate neuropathic pain. Finally, rescue assays demonstrated that the activation of Wnt/β-catenin signaling pathway or MAL2 upregulation reversed the inhibitory influence of miR-216b-5p on neuropathic pain. In conclusion, miR-216b-5p alleviated neuropathic pain in rats by targeting MAL2 to inactivate the Wnt/β-catenin signaling pathway, which may provide novel insight for the therapy of neuropathic pain.