Shao Jinping, Cao Jing, Wang Jiannan, Ren Xiuhua, Su Songxue, Li Ming, Li Zhihua, Zhao Qingzan, Zang Weidong
Department of Anatomy, Basic Medical College, Zhengzhou University, Zhengzhou, China.
Department of Anatomy, Basic Medical College, Zhengzhou University, Zhengzhou, China
Mol Pain. 2016 Oct 19;12. doi: 10.1177/1744806916671523. Print 2016.
Voltage-gated sodium channels, which are involved in pain pathways, have emerged as major targets for therapeutic intervention in pain disorders. Nav1.7, the tetrodotoxin-sensitive voltage-gated sodium channel isoform encoded by SCN9A and predominantly expressed in pain-sensing neurons in the dorsal root ganglion, plays a crucial role in nociception. MicroRNAs are highly conserved, small non-coding RNAs. Through binding to the 3' untranslated region of their target mRNAs, microRNAs induce the cleavage and/or inhibition of protein translation. Based on bioinformatics analysis using TargetScan software, we determined that miR-30b directly targets SCN9A To investigate the roles of Nav1.7 and miR-30b in neuropathic pain, we examined changes in the expression of Nav1.7 in the dorsal root ganglion by miR-30b over-expression or knockdown in rats with spared nerve injury. Our results demonstrated that the expression of miR-30b and Nav1.7 was down-regulated and up-regulated, respectively, in the dorsal root ganglion of spared nerve injury rats. MiR-30b over-expression in spared nerve injury rats inhibited SCN9A transcription, resulting in pain relief. In addition, miR-30b knockdown significantly increased hypersensitivity to pain in naive rats. We also observed that miR-30b decreased Nav1.7 expression in PC12 cells. Taken together, our results suggest that miR-30b plays an important role in neuropathic pain by regulating Nav1.7 expression. Therefore, miR-30b may be a promising target for the treatment of chronic neuropathic pain.
电压门控钠通道参与疼痛信号传导通路，已成为疼痛性疾病治疗干预的主要靶点。Nav1.7是由SCN9A编码的对河豚毒素敏感的电压门控钠通道亚型，主要表达于背根神经节的痛觉感受神经元中，在伤害性感受中起关键作用。微小RNA是高度保守的小非编码RNA。通过与靶mRNA的3'非翻译区结合，微小RNA可诱导靶mRNA的切割和/或抑制蛋白质翻译。基于使用TargetScan软件的生物信息学分析，我们确定miR-30b直接靶向SCN9A。为了研究Nav1.7和miR-30b在神经性疼痛中的作用，我们通过在 spared nerve injury大鼠中过表达或敲低miR-30b来检测背根神经节中Nav1.7表达的变化。我们的结果表明，在 spared nerve injury大鼠的背根神经节中，miR-30b的表达下调，而Nav1.7的表达上调。在 spared nerve injury大鼠中过表达miR-30b可抑制SCN9A转录，从而缓解疼痛。此外，敲低miR-30b可显著增加正常大鼠对疼痛的超敏反应。我们还观察到miR-30b可降低PC12细胞中Nav1.7的表达。综上所述，我们的结果表明miR-30b通过调节Nav1.7的表达在神经性疼痛中起重要作用。因此，miR-30b可能是治疗慢性神经性疼痛的一个有前景的靶点。
