IMPACT OF EARLY EXPERIENCE ON VULVOVAGINAL SENSITIVITY IN ADULT MOUSE

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 早期的生活经历已被证明对慢性疼痛的患病率有深远的影响。早产儿暴露于许多应激源，包括反复的侵入性手术和长时间的母体分离，往往后来对痛苦事件产生不利的行为和生理反应，以及一些功能性疼痛障碍的更高发生率。经历压力或反复痛苦程序的新生大鼠在成年后同样会出现慢性疼痛。这项研究旨在1)确定新生儿应激或刺激如何影响外阴和阴道的敏感性和感觉神经支配，2)使用一种方法选择性地移除负责疼痛感觉的神经作为治疗人类外阴疼痛的临床前试验。据估计，外阴疼痛影响15%的女性，临床上定义为外阴的慢性不适或疼痛，通常发生为灼热、刺痛或疼痛。对供应该区域的神经的潜在变化知之甚少，目前的文献中也没有动物模型。这些研究的成功完成不仅将提供第一个已发表的外阴疼痛模型，而且也是开发一类新的化合物的第一步，这种化合物可以在不影响正常感觉的情况下缓解慢性盆腔疼痛。考虑到外阴疼痛与其他慢性盆腔疼痛综合征如子宫内膜异位症、肠易激综合征和间质性膀胱炎的高度共患性，化学消融这一群体的伤害性感受器也可以缓解这些症状。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Early life experience has been shown to have a profound impact on the prevalence of chronic pain. Prematurely born infants are exposed to numerous stressors, including repeated invasive procedures and prolonged periods of maternal separation, and often later develop adverse behavioral and physiological responses to painful events, as well as have a higher incidence of some functional pain disorders. Newborn rats that undergo stress or repeated painful procedures similarly develop chronic pain as adults. This study is designed to 1) determine how neonatal stress or irritation affects the sensitivity and sensory innervation of the vulva and vagina, and 2) employ a method to selectively remove the nerves responsible for pain sensations as a preclinical test for treating vulvodynia in humans. Vulvodynia affects an estimated 15% of women and is clinically defined as chronic discomfort or pain of the vulva, often occurring as burning, stinging or soreness. Little is known regarding potential changes in the nerves that supply this region and no animal models exist in the current literature. Successful completion of these studies will not only provide the first published model of vulvodynia, but is also the first step in developing a new class of compounds that alleviates chronic pelvic pain without affecting normal sensations. Considering the high degree of comorbidity between vulvodynia and other chronic pelvic pain syndromes, e.g. endometriosis, irritable bowel syndrome and interstitial cystitis, chemical ablation of this population of nociceptors could also alleviate symptoms of these syndromes, as well.