子宫内膜异位症疼痛的中枢敏化机制研究

Endometriosis, a common disease in women of childbearing age, is associated with various pelvic pain symptoms in 70-80% of women, impairing woman's health-related quality of life and health care cost. It is an enigmatic disease with poor response to conservative treatment. Central sensitization is defined as an increase in the excitability of the central nevors systom so that normal inputs evoke exaggerated responses. And resting-state function magnatic resonance imaging (rfMRI) is a powel tool for investigating spontaneous neural activity based on resting state blood oxygen level dependence signals, and has been widely used in elucidating the brain neurophysiology. To the best of our known, few studies have been performed on central sensitization in endometriosis associated pain symptoms. Thus, our objectives are to investigate the central sensitization mechanisms in endometriosis. Firstly, we will utilize rfMRI to identify brain networks signature related to endometriosis associated pain. Secondly, a rat model with uterine autotransplanting, or fat will be developed, followed by behavioral and electrophysiological tests. Thirdly, rfMRI imaging will be conducted on both rat models. Fourthly, to explore the molecular mechanisms underlying central sensitization, differentially expressed genes of the abnormally activated brain regions will be analyzed using the microarray and bioinformatics. Finally, the role of estrogen and progesterone on central sensitizatin will be explored. Our study will provide new insights into the mechanisms underlying endometriosis associated pain symptoms, thus opening new potential avenues to conquer of this catastrophic disease.

子宫内膜异位症是育龄期妇女常见病，70-80％的患者有不同类型的疼痛，严重影响女性的健康和生活质量，花费大量医疗资源。其病因不明，治疗效果不佳。中枢敏化和静息态脑功能成像（rfMRI）均是当前疼痛研究的热点，前者指脊髓及脊髓上(如丘脑、脑干、大脑皮层)阶段对疼痛传递反应的放大，后者可以观察静息状态下大脑内部发生的血氧水平信号的自发调节变化，但在内异症研究中尚属空白。本研究旨在开展内异症的中枢敏化机制研究。主要内容：1）rfMRI解析内异症合并重度疼痛患者静息状态下的脑功能解剖图谱；2）自体子宫移植法构建内异症大鼠模型（ENDO）；3）rfMRI观察ENDO大鼠疼痛模型静息状态下的脑功能活动；4）基因组表达谱芯片探索ENDO大鼠疼痛模型异常激活脑区的分子机制；5）分别从脊髓及脊髓上阶段探讨雌、孕激素在中枢敏化中的作用。该研究将为深入探讨内异症疼痛的发病机制、为寻找新的治疗靶点提供理论依据.