Department of Histology and Embryology, Medical College, Nanchang University, Bayi Road 461, Nanchang, 330006, People's Republic of China.
Nanchang Joint Programme, Queen Mary University of London, London, E1 4NS, UK.
Neurochem Res. 2018 Jun;43(6):1143-1149. doi: 10.1007/s11064-018-2529-4. Epub 2018 May 7.
MicroRNAs have been implicated in nerve injury and neuropathic pain. In the previous study we had shown that miR-96 can attenuate neuropathic pain through inhibition of Nav1.3. In this study, we investigated the role of miR-183, a same cluster member of microRNA with miR-96, in neuropathic pain and its potential mechanisms. We found that the expression level of miR-183-5p in dorsal root ganglion was decreased with the development of neuropathic pain induced by chronic constriction sciatic nerve injury (CCI). By contrast, the TREK-1, a K channel, was increased. Further investigation identified that intrathecal injection of miR-183-5p mimic efficiently ameliorated neuropathic pain and inhibited the expression of TREK-1, a predicted target gene of miR-183-5p. Luciferase assays confirmed the binding of miR-183-5p and TREK-1. In addition, over-expression of TREK-1 blocked the roles of miR-183-5p in neuropathic pain. Our findings suggested that miR-183-5P participated in the regulation of CCI-induced neuropathic pain through inhibiting the expression of TREK-1.
微小 RNA 已被牵涉到神经损伤和神经性疼痛中。在之前的研究中,我们已经表明 miR-96 可以通过抑制 Nav1.3 来减轻神经性疼痛。在这项研究中,我们研究了 microRNA 与 miR-96 同一家族的成员 miR-183 在神经性疼痛及其潜在机制中的作用。我们发现,miR-183-5p 的表达水平在背根神经节中随着慢性缩窄性坐骨神经损伤(CCI)引起的神经性疼痛的发展而降低。相比之下,TREK-1,一种 K 通道,增加了。进一步的研究确定,鞘内注射 miR-183-5p 模拟物有效地改善了神经性疼痛,并抑制了 TREK-1 的表达,TREK-1 是 miR-183-5p 的一个预测靶基因。荧光素酶测定证实了 miR-183-5p 和 TREK-1 的结合。此外,TREK-1 的过表达阻断了 miR-183-5p 在神经性疼痛中的作用。我们的研究结果表明,miR-183-5P 通过抑制 TREK-1 的表达参与了 CCI 诱导的神经性疼痛的调节。