Neuropathic pain is clinically unsatisfactorily treated because of unclear mechanisms. The present study aims to explore the concrete mechanisms underlying the alleviation of resveratrol-activated silent information regulator 1 (Sirt1) to chronic constriction injury (CCI)-induced neuropathic pain. CCI surgery was conducted to the unilateral sciatic nerve of male Sprague-Dawley rats to induce neuropathic pain experimentally. Resveratrol with or without miR-182 antagomir were administered to CCI rats via intrathecal catheter. Behavioral tests including paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were conducted to explore mechanical allodynia and thermal hyperalgesia. Western blot, qRT-PCR were used to detect the expression levels of Sirt1, miR-182, and Nav1.7 in CCI dorsal root ganglions (DRGs). CCI rats displayed lower PWT and PWL compared with the sham control. Also, the CCI DRGs displayed lower Sirt1 and miR-182 expression as well as higher Nav1.7 expression, which would be almost reversed by resveratrol treatment for 4 successive days. We also found that miR-182 expression inhibition erased the analgesia effect of resveratrol to CCI-induced neuropathic pain possibly through upregulating Nav1.7 expression. In summary, resveratrol alleviated CCI-induced neuropathic pain, possibly through activating Sirt1 to suppress Nav1.7 expression via upregulating miR-182 expression in CCI DRGs.

中文翻译：

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白藜芦醇激活 Sirt1 可通过 miR-182 抑制 DRG 中 Nav1.7 的表达，并减轻大鼠的神经性疼痛。


由于机制尚不清楚，神经性疼痛在临床上的治疗效果并不令人满意。本研究旨在探讨白藜芦醇激活的沉默信息调节因子1（Sirt1）缓解慢性压迫性损伤（CCI）引起的神经病理性疼痛的具体机制。对雄性 Sprague-Dawley 大鼠的单侧坐骨神经进行 CCI 手术，以实验性诱导神经性疼痛。通过鞘内导管向 CCI 大鼠施用含有或不含 miR-182 antagomir 的白藜芦醇。进行包括缩爪阈值（PWT）和缩爪潜伏期（PWL）在内的行为测试，以探讨机械异常性疼痛和热痛觉过敏。采用Western blot、qRT-PCR检测CCI背根神经节（DRG）中Sirt1、miR-182和Nav1.7的表达水平。与假手术对照组相比，CCI 大鼠表现出较低的 PWT 和 PWL。此外，CCI DRGs 显示出较低的 Sirt1 和 miR-182 表达以及较高的 Nav1.7 表达，这几乎可以通过连续 4 天的白藜芦醇治疗来逆转。我们还发现，miR-182 表达抑制可能通过上调 Nav1.7 表达来消除白藜芦醇对 CCI 诱导的神经性疼痛的镇痛作用。总之，白藜芦醇可能通过上调 CCI DRG 中 miR-182 的表达来激活 Sirt1 抑制 Nav1.7 的表达，从而减轻 CCI 诱导的神经性疼痛。