Neural Mechanisms of Gynecological Pain

描述(由申请者提供)：该项目的长期目标是促进对女性骨盆疼痛神经机制的了解。这里的研究重点是子宫内膜异位症，这是一种子宫内膜在子宫外异常生长的疾病，并合成许多物质，如细胞因子和前列腺素。症状包括生育力下降和几种盆腔疼痛，包括性交困难(阴道肥大)。子宫内膜异位症的大鼠模型，即子宫组织被自体移植到腹部并形成囊肿，已被用于研究生育力下降。自体移植也会引起阴道痛觉过敏。在大鼠身上进行了四项研究，以检验关于这种痛觉过敏机制的假说。研究1和2将检验这样的假设，即痛觉过敏依赖于雌激素，并需要持续存在囊肿。这些研究将通过确定控制激素水平或切除包囊对痛敏的影响来完成，这将使用阴道伤害性行为指标进行评估。研究3将验证这一假说，即包囊通过自身诱导的神经供应向中枢神经系统发送伤害性信息，从而导致阴道痛觉过敏。这项研究将使用传入和自主神经传出神经纤维的选择性标记来表征不同实验条件下(手术后时间；发情期)包囊的感觉和交感神经支配。研究4将验证这样的假设，即大麻素通过CB1受体调节包囊产生促和抗炎的细胞因子和前列腺素，从而导致痛觉过敏。这项研究将使用酶联免疫吸附试验来比较在手术后不同时间和不同发情阶段用大麻素激动剂、拮抗剂和控制剂处理后包囊细胞因子和前列腺素的产生。希望这一结果将有助于我们了解子宫内膜异位症的病因，并改进女性和男性盆腔和其他内脏疼痛的治疗策略。

DESCRIPTION (provided by applicant): The long-term goal of this program is to advance understanding of neural mechanisms of pelvic pain in females. The studies here focus on endometriosis, a disease in which endometrial growths occur abnormally outside the uterus and synthesize many substances such as cytokines and prostaglandins. Symptoms include reduced fertility and several pelvic pains, including dyspareunia (vaginal hyperagesia). A rat model of endometriosis, in which uterine tissue is autotransplanted into the abdomen and forms cysts, has been used to study reduced fertility. The autotransplants also induce vaginal hyperalgesia. Four studies in rats are proposed to test hypotheses concerning mechanisms underlying this hyperalgesia. Studies 1 and 2 will test the hypotheses that the hyperalgesia depends on estrogen and requires continued presence of the cysts. The studies will be done by determining how manipulating hormone levels or excising the cysts affects the hyperalgesia, which will be assessed using behavioral measures of vaginal nociception. Study 3 will test the hypothesis that the cysts contribute to vaginal hyperalgesia by sending nociceptive information to the central nervous system via their own induced nerve supply. The study will be done using selective markers for afferent and autonomic efferent nerve fibers to characterize the cysts' sensory and sympathetic innervation under different experimental conditions (time after surgery; estrous stage). Study 4 will test the hypothesis that cannabinoids contribute to the hyperalgesia by regulating, via CB1 receptors, the cysts' production of }ro- and anti-inflammatory cytokines and prostaglandins. The study will be done using enzyme-linked mmunosorbent assays to compare the cysts' production of cytokines and prostaglandins after treatments with cannabinoid agonist, antagonist, and control agents at different times after surgery and in different estrous stages. It is hoped that the results will contribute to our knowledge of the etiology of endometriosis and to improving treatment strategies for pelvic and other visceral pains in both women and men.