Neuropathic pain is chronic pain and has few effective control strategies. Studies have demonstrated that microRNAs have functions in neuropathic pain. However, no study has been conducted to demonstrate the role and mechanism of microRNA (miR)-31-5p in neuropathic pain. Accordingly, this study sought to determine the pathological role of miR-31-5p in chronic constriction injury (CCI) -induced neuropathic pain mouse models. We used CCI surgery to establish mouse neuropathic pain model. Behavioral tests were performed to evaluate pain sensitivity of mice. Expressions of miR-31-5p and inflammatory cytokines in dorsal root ganglion (DRG) were examined by polymerase chain reaction. Animals or cells were received with/without miR-31-5p mimic or inhibitor to investigate its role in neuropathic pain. The mechanism of miR-31-5p was assayed using western blotting, immunofluorescence staining and dual-luciferase reporter assay. We found that CCI led to a significant decrease in miR-31-5p levels. Knockout of miR-31-5p and administration of miPEP31 exacerbated pain in C57BL/6 mice. Meanwhile, miR-31-5p overexpression increased the paw withdrawal threshold and latency. TRAF6 is one of the target gene of miR-31-5p, which can trigger a complex inflammatory response. TRAF6 was associated with pain and that reducing the DRG expression of TRAF6 could alleviate pain. In addition, miR-31-5p overexpression inhibited the TRAF6 expression and reduced the neuroinflammatory response. All the results reveal that miR-31-5p could potentially alleviate pain in CCI mouse models by inhibiting the TRAF6 mediated neuroinflammatory response. MiR-31-5p upregulation is highlighted here as new target for CCI treatment.

中文翻译：

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MiR-31-5p 通过 TRAF6 调节神经性疼痛中的神经炎症反应

神经性疼痛是慢性疼痛，几乎没有有效的控制策略。研究表明 microRNA 在神经性疼痛中具有作用。然而，目前尚无研究证明 microRNA (miR)-31-5p 在神经性疼痛中的作用和机制。因此，本研究试图确定 miR-31-5p 在慢性压迫性损伤 (CCI) 诱导的神经性疼痛小鼠模型中的病理作用。我们采用CCI手术建立小鼠神经病理性疼痛模型。进行行为测试来评估小鼠的疼痛敏感性。通过聚合酶链反应检测背根神经节（DRG）中 miR-31-5p 和炎症细胞因子的表达。接受有/没有 miR-31-5p 模拟物或抑制剂的动物或细胞，以研究其在神经性疼痛中的作用。使用蛋白质印迹、免疫荧光染色和双荧光素酶报告基因测定来分析 miR-31-5p 的机制。我们发现 CCI 导致 miR-31-5p 水平显着下降。敲除 miR-31-5p 并给予 miPEP31 会加剧 C57BL/6 小鼠的疼痛。同时，miR-31-5p 过表达增加了缩爪阈值和潜伏期。TRAF6是miR-31-5p的靶基因之一，可以触发复杂的炎症反应。TRAF6与疼痛相关，减少TRAF6的DRG表达可以减轻疼痛。此外，miR-31-5p过表达抑制TRAF6表达并减少神经炎症反应。所有结果表明，miR-31-5p 可以通过抑制 TRAF6 介导的神经炎症反应来减轻 CCI 小鼠模型的疼痛。这里强调 MiR-31-5p 上调作为 CCI 治疗的新目标。