Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 20080, China.
Biol Direct. 2024 Jan 24;19(1):10. doi: 10.1186/s13062-023-00434-1.
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.
神经病理性疼痛是一种慢性疼痛，目前控制策略有限。研究表明 microRNAs 在神经病理性疼痛中具有功能。然而，目前尚无研究表明 microRNA (miR)-31-5p 在神经病理性疼痛中的作用和机制。因此，本研究旨在确定 miR-31-5p 在慢性缩窄性损伤（CCI）诱导的神经病理性疼痛小鼠模型中的病理作用。
我们使用 CCI 手术建立小鼠神经病理性疼痛模型。通过行为测试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。用/不用 miR-31-5p 模拟物或抑制剂处理动物或细胞，以研究其在神经病理性疼痛中的作用。使用 Western blot、免疫荧光染色和双荧光素酶报告基因检测来检测 miR-31-5p 的作用机制。
我们发现 CCI 导致 miR-31-5p 水平显著降低。miR-31-5p 敲除和 miPEP31 给药加重 C57BL/6 小鼠的疼痛。同时，miR-31-5p 过表达增加了足底撤回阈值和潜伏期。TRAF6 是 miR-31-5p 的靶基因之一，可引发复杂的炎症反应。TRAF6 与疼痛有关，减少 DRG 中 TRAF6 的表达可以缓解疼痛。此外，miR-31-5p 过表达抑制 TRAF6 的表达并减少神经炎症反应。
所有结果表明，miR-31-5p 通过抑制 TRAF6 介导的神经炎症反应，可能减轻 CCI 小鼠模型中的疼痛。miR-31-5p 的上调在这里被强调为 CCI 治疗的新靶点。
