Neural Mechanisms of Gynecological Pain

描述（由申请人提供）：这个项目的长期目标是促进对女性骨盆疼痛的神经机制的理解。子宫内膜异位症是一种子宫内膜在子宫外异常生长并合成多种物质如细胞因子和前列腺素的疾病。症状包括生育能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，其中子宫组织被自体移植到腹部并形成囊肿，已被用于研究生育能力降低。自体移植物也会引起阴道痛觉过敏。提出了四项大鼠研究，以测试有关这种痛觉过敏机制的假设。研究1和研究2将检验痛觉过敏依赖于雌激素并需要囊肿持续存在的假设。研究将通过确定操纵激素水平或切除囊肿如何影响痛觉过敏来完成，这将通过阴道伤害感受的行为测量来评估。研究3将验证囊肿通过其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的假设。本研究将使用传入和自主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）囊肿的感觉和交感神经支配。研究4将验证大麻素通过CB1受体调节囊肿中抗炎和抗炎细胞因子和前列腺素的产生而导致痛觉过敏的假设。该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期使用大麻素激动剂、拮抗剂和对照剂治疗后囊肿细胞因子和前列腺素的产生。希望这些结果将有助于我们了解子宫内膜异位症的病因，并改善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.