女性盆底重建术后慢性盆腔痛的中枢发病机制

Postoperative chronic pelvic pain is a common complication of pelvic floor reconstruction and a variety of methods effects are not obvious, seriously affecting the patients' quality of life. Currently the mechanism of postoperative chronic pelvic pain is not clear, but studies including our previous study found that chronic pelvic pain patients with brain changes in the structure and function of the pain matrix and central sensitization, and also found that these changes secondary to chronic pelvic pain increased the pain in patients and could predispose to the development of another. In addition. All of these suggest that there may have the central mechanisms in postoperative chronic pelvic pain occurred. We hypothesized that postoperative chronic pelvic pain of pelvic reconstructive surgery can lead to the changes of neuronal gene expression in brain regions of pain matrix , so the distribution, the multiplication and the apoptosis of these neurons will change, causing central sensitization. In this study, we will undertake a longitudinal studies to research perioperative PFD patients’ brain functional magnetic resonance (fMRI) in resting and tasks state to explore the mechanism of the postoperative chronic pelvic pain’s development and mitigation. In addition, we will compare findings from whole genome expression profile of postoperative chronic pelvic pain patients' blood with whole genome expression profile of pain matrix and blood of CPPS model mice.Our study will expect to identify and clarify the central mechanisms of postoperative chronic pelvic pain, and to seek new therapeutic interventions and targets of postoperative chronic pelvic pain.

女性盆底重建术后慢性盆腔痛是盆底重建手术后常见并发症，部分患者疼痛治疗效果差，严重影响生活质量。我们前期研究发现，盆底重建术后盆腔疼痛患者大脑内疼痛矩阵脑区出现皮质变薄和功能异常，且这些变化增加了患者疼痛性疾病的易感性，但机制不明。由此我们提出假说:盆底重建术后慢性盆腔疼痛可以导致疼痛矩阵脑区神经元基因表达改变，使得这些神经元细胞的分布、增殖、凋亡发生改变，从而引起患者中枢痛觉敏化而导致慢性疼痛。本研究拟通过对围术期患者大脑静息态和任务态功能性磁共振（fMRI）的纵向研究以及比较盆底重建术后慢性盆腔痛患者、慢性盆腔痛模型小鼠与对照组外周血基因表达谱与疼痛矩阵脑区基因表达谱演变的相互关系，探索疼痛矩阵的变化在盆底重建术后慢性盆腔痛中的作用机制，阐明疼痛矩阵变化脑区的基因表达谱变化特征，为盆底重建术后慢性盆腔痛寻求新的干预手段和靶点。

女性盆底重建术后慢性盆腔痛是盆底重建手术后常见并发症，部分患者疼痛治疗效果差，严重影响生活质量。本研究首先从临床入手，通过对盆底功能障碍患者围术期大脑静息态和任务态功能性磁共振（fMRI）的纵向研究发现了慢性盆腔痛患者各脑区功能相对正常患者激活模式不同，疼痛患者在楔前叶皮层，扣带回，角回，枕外侧皮层，内侧前额叶，额上、中、下回等区域的正激活减弱，在脑岛，脑干，丘脑，海马，杏仁核，尾状核，壳核，苍白球等区域的负激活减弱。两组患者各脑区之间的功能连接也存在较大差异。进一步地，通过建立SD大鼠慢性疼痛中枢敏化模型验证了痛觉过敏动物大脑基底节区MRI信号明显增强，CCL2在痛觉过敏动物外周血外泌体，盆腔血管内皮细胞及脑脊液中表达均升高。最后通过细胞实验，发现CCL2可能是通过激活Notch2信号通路从而在中枢敏化过程中起着重要作用。本研究找出了盆底术后慢性盆腔中枢敏化的重要靶点，可能为后续对盆腔疼痛的靶向治疗研究提供新的依据。