NEURAL MECHANISMS OF GYNECOLOGICAL PAIN

描述（改编自申请人摘要）： 拟议的研究是为了提高对神经机制的理解， 妇科疼痛 这些研究使用了行为和电生理学 方法来表征逃避行为和中枢神经系统活动引起的骨盆 在各种正常和病理条件下对雌性大鼠的器官刺激 条件 今后五年的具体目标侧重于 阴道痛觉过敏（VAGH），并将测试三个假设。 (1)生殖衰老和VAGH：女性的阴道敏感性 绝经后增加，产生VAGH。 这种VAGH被认为是由于 雌激素流失对阴道组织的影响 的假设 衰老-VAGH与雌激素水平低下有关， 阴道的物理特性将在大鼠中通过使用行为 方法在清醒的大鼠中研究如何逃避对阴道扩张的反应 以及阴道张力如何随着大鼠的衰老而变化， 是荷尔蒙控制的结果 (2)子宫内膜异位症和VAGH：子宫外有活力的子宫内膜组织， 女性与不孕症和盆腔疼痛有关，包括VAGH。 由于雌激素是异位子宫内膜生存所必需的， 方法和激素操作将用于大鼠模型， 子宫内膜异位症，以检验假设，子宫内膜异位症-VAGH，相反， 衰老-VAGH依赖于雌激素，不依赖于阴道张力。 (3)CNS机制：尽管大鼠的感觉传入神经 女性生殖道传递高度特异性和 在脊髓中的许多神经元将拓扑结构组织的信息传递到CNS， 脊髓和丘脑对盆腔器官的刺激反应一致， 皮肤，并且响应可以根据改变CNS控制而改变 因素 更令人惊讶的是，这种情况似乎也适用于 另外两个入口处的神经元将骨盆信息传递到中枢神经系统， 薄束核和孤束核，表明这两个门脉核 值得纳入，沿着脊髓，在中枢神经系统疼痛的研究 机制等 因此，电生理学研究将比较 薄肌神经元对盆腔器官和皮肤刺激的反应 孤束核和脊髓中的孤束核也随之改变 动情状态、衰老-VAGH和衰老-VAGH。

DESCRIPTION (adapted from applicants abstract): The long-range goal of the proposed research is to improve understanding of the neural mechanisms of gynecological pain. The studies use behavioral and electrophysiological methods to characterize escape behaviors and CNS activity elicited by pelvic organ stimulation in female rats under various normal and pathological conditions. Specific aims for the next 5 years focus on mechanisms of vaginal hyperalgesia (VAGH) and will test three hypotheses. (1) Reproductive senescence and VAGH: Vaginal sensitivity in women increases after menopause to produce VAGH. This VAGH is thought to be due to the effects of estrogen loss on vaginal tissue. The hypothesis that senescence-VAGH is associated with hypoestrogenic-conditions and changes in physical properties of the vagina will be tested in rats by using behavioral methods in awake rats to study how escape responses to vaginal distension and how vaginal tone both changes as the rats age through senescence and following hormonal manipulations. (2) Endometriosis and VAGH: Viable endometrial tissue outside the uterus in women is associated with infertility and pelvic pain, including VAGH. Because estrogen is necessary for ectopic endometrial viability, behavioral methods and hormonal manipulations will be used on a rat model of endometriosis to test the hypothesis that endometriosis-VAGH, in contrast to senescence-VAGH, depends upon estrogen and is independent of vaginal tone. (3) CNS mechanisms: Despite the fact that sensory afferents of the rat female reproductive tract convey highly specific and topographically-organized information to the CNS, many neurons in the spinal cord and thalamus respond convergently to stimulation of pelvic organs and skin, and the responses can change depending on changing CNS control factors. Even more surprisingly, this situation appears also to apply to neurons in the two other ports-of-entry for pelvic information to the CNS, the gracile and solitary nuclei, suggesting that these two portal nuclei warrant inclusion, along with the spinal cord, in studies of CNS pain mechanisms. Accordingly, electrophysiological studies will compare how responses to stimulation of pelvic organs and skin by neurons in the gracile and solitary nuclei, as well as in the spinal cord, change as a consequence of estrous state, senescence-VAGH, and endometrious-VAGH.