NEURAL MECHANISMS OF GYNECOLOGICAL PAIN

描述(改编自申请者摘要)： 建议的研究是为了提高对高血压的神经机制的理解。 妇科疼痛。这项研究使用了行为学和电生理学 骨盆逃逸行为和中枢神经系统活动的表征方法 不同正常和病理状态下雌性大鼠的器官刺激 条件。未来5年的具体目标侧重于 阴道痛觉过敏(VAGH)并将检验三个假设。 (1)生殖衰老与阴道促性腺激素：女性的阴道敏感性 绝经后增加以产生VAGH。这一次VAGH被认为是 雌激素丢失对阴道组织的影响。假设 衰老-VAGH与雌激素水平低下的条件和 阴道的物理性质将在大鼠身上进行测试，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 以及随着大鼠年龄的增长，阴道张力是如何变化的 在荷尔蒙控制之后。 (2)子宫内膜异位症与VAGH：子宫外可存活的子宫内膜组织 女性与不孕不育和盆腔疼痛有关，包括VAGH。 因为雌激素是异位内膜存活所必需的，所以行为 方法和激素操作将用于一种大鼠模型 以检验子宫内膜异位症-VAGH的假说，与 衰老-VAGH，依赖于雌激素，不依赖于阴道张力。 (3)中枢神经系统机制：尽管大鼠的感觉传入 女性生殖道传递高度特异性和 将地形图组织的信息传递到中枢神经系统，脊髓中的许多神经元 脊髓和丘脑对刺激盆腔器官和 皮肤，并且响应可以根据CNS控制的改变而改变 各种因素。更令人惊讶的是，这种情况似乎也适用于 另外两个进入中枢神经的盆腔信息入口的神经元， 纤细而孤立的核，表明这两个门静脉核 在中枢神经系统疼痛的研究中，应包括脊髓 机械装置。相应地，电生理学研究将比较 股薄区神经元对刺激盆腔器官和皮肤的反应 和孤束核，以及脊髓中的变化，结果是 动情期、衰老-VAGH、子宫内膜-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.