miR-32在疼痛缓解中的作用与机制研究

The incidence of chronic pain after cesarean is significantly lower than other surgery with similar trauma, which prompting a protection mechanism of delivery to relieve pain. miR-32, a highly homologous miRNA between human and rat identified from differential miRNA expression profile, was specially high-expressed in the doral root ganglion（DRG）of postpartum pain rat model, which hasn't been reported in pain relief. Specific up-expression of miR-32 in the DRG tissue can notably raise the pain threshold of the nonpregnant pain rat model, prompting the potential role of miR-32 in pain relief. Preliminary experiments demonstrated that NRG1 was the target gene of miR-32. Literatures have reported that NRG1 secreted by DRG neurons participated in pain via regulating the function of microglial cells. Meanwhile down-regulation of NRG1 is involved in the relief of postpartum pain, prompting the potential role of miR-32 in pain relief via regulating NRG1 expression and secretion. The study will estimate the influence of knock-down and over-expression of miR-32 on neuropathic pain relief; use rescue strategies to explore the underlying mechanism of pain relief via regulating NRG1 expression by miR-32. This study will provide a new target for postoperative pain relief.

剖宫产术后慢性疼痛发生率远低于与其具有相似组织创伤的外科手术，提示分娩过程存在一种缓解疼痛机制。miR-32是我们借助芯片筛选获得的、人鼠同源、显著高表达于产后疼痛大鼠模型背根神经节（DRG）组织的miRNA，目前未见其在疼痛缓解中的报道。前期发现，在非妊娠疼痛大鼠模型中上调miR-32表达能显著提高痛阈，提示疼痛缓解；预实验还提示NRG1为其潜在靶标，已报道NRG1由DRG神经元细胞分泌后提呈给小胶质细胞参与疼痛发生，其下调与产后疼痛缓解相关，提示miR-32通过调控NRG1表达影响其分泌参与疼痛缓解。研究拟：采用过表达和表达沉默策略，系统论证miR-32在疼痛缓解中的作用；以NRG1为切入点，通过挽救策略，探讨miR-32调控NRG1表达缓解疼痛的分子机制。本研究有望为术后疼痛缓解提供潜在新靶点。