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.

MicroRNA (miRNA) 是神经元功能的重要调节因子，参与神经性疼痛的发生。据报道，MiR-216b-5p 参与许多人类疾病的进展。然而，miR-216b-5p在神经病理性疼痛中的生物学效应和调控机制尚未被发现。在本研究中，我们旨在通过慢性压迫性损伤（CCI）方法构建神经病理性疼痛大鼠模型，探讨miR-216b-5p在神经病理性疼痛中的功能。 miR-216b-5p 在 CCI 大鼠模型中被发现下调，表明 miR-216b-5p 在神经性疼痛中发挥作用。接下来，证明 miR-216b-5p 过表达可减轻 CCI 大鼠的神经性疼痛和神经炎症。此外，miR-216b-5p过表达被发现抑制Wnt/β-catenin信号通路，髓磷脂和淋巴细胞蛋白2（MAL2）是miR-216b-5p的下游靶点。 MiR-216b-5p 通过下调 MAL2 使 Wnt/β-catenin 信号通路失活。此外，MAL2 敲低被证实可以减轻神经性疼痛。最后，救援实验表明，Wnt/β-catenin 信号通路的激活或 MAL2 的上调可逆转 miR-216b-5p 对神经性疼痛的抑制作用。总之，miR-216b-5p通过靶向MAL2灭活Wnt/β-catenin信号通路来减轻大鼠神经病理性疼痛，这可能为神经病理性疼痛的治疗提供新的见解。