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.

神经性疼痛是一种毁灭性疾病，对目前可用的镇痛剂存在耐受性。据报道，MicroRNA 参与了神经性疼痛的调节，但 miR-216a-5p 在神经性疼痛中的生物学作用仍不清楚。在本研究中，我们构建了神经性疼痛的 CCI 大鼠模型。我们的研究结果表明，miR-216a-5p 在 CCI 大鼠中的表达下调，并且通过 miR-216a-5p 过表达改善了 CCI 大鼠的机械异常性疼痛和热痛觉过敏，表明 miR-216a-5p 过表达减轻了神经性疼痛。此外，ELISA 显示 miR-216a-5p 过表达抑制 IL-6、TNF-α 和 IL-1β 的浓度和 mRNA 表达，并抑制小胶质细胞浸润，表明 miR-216a-5p 过表达抑制神经炎症。除了，我们发现 miR-216a-5p 上调使 Wnt/β-catenin 信号通路失活。此外，KDM3A 是 miR-216a-5p 的下游靶点，KDM3A 敲低可减轻神经性疼痛。最后，通过救援试验，我们发现 KDM3A 通过 Wnt/β-catenin 信号通路抵消了 miR-216a-5p 介导的神经性疼痛调节。综上所述，我们的研究证实了 miR-216a-5p 通过靶向 KDM3A 和灭活 Wnt/β-catenin 信号通路来减轻大鼠的神经性疼痛，这可能为治疗神经性疼痛开辟了一条新的有效途径。我们发现 KDM3A 通过 Wnt/β-catenin 信号通路抵消了 miR-216a-5p 介导的神经性疼痛调节。综上所述，我们的研究证实了 miR-216a-5p 通过靶向 KDM3A 和灭活 Wnt/β-catenin 信号通路来减轻大鼠的神经性疼痛，这可能为治疗神经性疼痛开辟了一条新的有效途径。我们发现 KDM3A 通过 Wnt/β-catenin 信号通路抵消了 miR-216a-5p 介导的神经性疼痛调节。综上所述，我们的研究证实了 miR-216a-5p 通过靶向 KDM3A 和灭活 Wnt/β-catenin 信号通路来减轻大鼠的神经性疼痛，这可能为治疗神经性疼痛开辟了一条新的有效途径。