Department of Anesthesiology, The Affiliated Huxi Hospital of Jining Medical College, Shanxian Central Hospital, Shanxian 274300, Shandong, China.
Department of Anesthesiology, The Affiliated Huxi Hospital of Jining Medical College, Shanxian Central Hospital, Shanxian 274300, Shandong, China.
Neurosci Res. 2021 Sep;170:255-264. doi: 10.1016/j.neures.2020.08.001. Epub 2020 Sep 2.
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.
神经病理性疼痛是一种破坏性疾病，目前可用的镇痛药物存在耐受现象。有研究报道 microRNAs 参与神经病理性疼痛的调节，但 miR-216a-5p 在神经病理性疼痛中的生物学作用尚不清楚。在本研究中，我们构建了 CCI 大鼠神经病理性疼痛模型。结果表明，CCI 大鼠 miR-216a-5p 表达下调，过表达 miR-216a-5p 可改善 CCI 大鼠的机械性痛觉过敏和热痛觉过敏，提示 miR-216a-5p 过表达可缓解神经病理性疼痛。此外，ELISA 结果显示，miR-216a-5p 过表达抑制了 IL-6、TNF-α 和 IL-1β 的浓度和 mRNA 表达，并抑制了小胶质细胞浸润，表明 miR-216a-5p 过表达抑制了神经炎症。此外，我们发现 miR-216a-5p 的上调使 Wnt/β-catenin 信号通路失活。进一步研究发现，KDM3A 是 miR-216a-5p 的下游靶基因，KDM3A 的敲低可减轻神经病理性疼痛。最后，通过挽救实验，我们发现 KDM3A 通过 Wnt/β-catenin 信号通路拮抗 miR-216a-5p 对神经病理性疼痛的调节作用。综上所述，本研究证实 miR-216a-5p 通过靶向 KDM3A 并抑制 Wnt/β-catenin 信号通路减轻大鼠神经病理性疼痛，为治疗神经病理性疼痛开辟了新的途径。
