Female Pelvic Pain, Hormones,and Neuroplasticity

荷尔蒙状态和阴道功能密切相关。绝经期生殖激素减少 导致阴道萎缩和干燥。更年期通常伴随着感觉迟钝的外阴痛， 由烧灼感和瘙痒感组成的综合症。与外阴前庭炎一起， 与早期口服避孕药的使用有关，外阴痛是一种未被认识到但重要的健康问题， 这个问题困扰着大约16%的美国成年女性。这些综合征的病因是不好的 虽然外阴前庭炎与疼痛感应纤维数量的增加有关，但这是可以理解的。没有 动物模型已经提供了更好的理解框架。最近，我们展示了 雌激素调节大鼠阴道神经支配卵巢切除术，接近人类更年期， 显著增加阴道感觉伤害感受器的数量，以及交感神经和副交感神经 轴突我们推测这是由于调节了阴道组织中营养因子的释放， 改变的神经支配将影响阴道功能的关键方面，包括血流，血管渗透性， 和疼痛敏感性。在目标1中，我们建议描述激素状态与 大鼠动情周期、妊娠期阴道神经支配与成年和幼年激素 局我们还确定人类阴道神经支配是否随激素状态而变化。目标2评估 轴突重塑的细胞机制通过决定生殖激素对 阴道靶组织以及感觉和自主神经元上。目的3检查分子机制 通过研究潜在营养因子的表达和功能相关性介导阴道重塑 因素在目标4中，我们评估了阴道神经重塑对血流的功能意义， 神经源性炎症和疼痛刺激的行为回避。这些研究是使用 细胞生物学、组织培养、分子生物学、生理学、药理学和行为学方法。的 这些实验的结果将提供深入了解的机制， 阴道神经支配的重塑，以及改变的神经支配是否可能导致阴道功能障碍。 此外，这些研究将提供一个更好的了解阴道神经之间的关系， 可塑性和外阴痛，并可能导致新的治疗，旨在扭转阴道感觉 超神经支配

Hormonal status and vaginal function are closely linked. Diminished reproductive hormones at menopause lead to vaginal atrophy and dryness. Menopause is often accompanied by dysesthetic vulvodynia, a pain syndrome consisting of burning and itching. Together with vulvar vestibulitis, an allodynia-like syndrome linked to early oral contraceptive use, vulvodynia represents an under-recognized but significant health problem, afflicting some 16% of the adult US female population. The etiology of these syndromes is poorly understood, although vulvar vestibulitis is associated with increased numbers of pain-sensing fibers. No animal models have been available to provide a better framework of understanding. Recently, we showed that estrogen regulates vaginal innervation in rats. Ovariectomy, which approximates human menopause, dramatically increases numbers of vaginal sensory nociceptors, as well as sympathetic and parasympathetic axons. We hypothesize that this is due to modulation of trophic factor release from vaginal tissues, and that altered innervation will influence key aspects of vaginal function, including blood flow, vascular permeability, and pain sensitivity. In aim 1 we propose to characterize the relationship between hormonal status and vaginal innervation in rats during the estrous cycle, pregnancy, and adult and juvenile hormone administration. We also determine if human vaginal innervation varies with hormonal state. Aim 2 assesses cellular mechanisms underlying axonal remodeling by determining effects of reproductive hormones on vaginal target tissue and on sensory and autonomic neurons. Aim 3 examines molecular mechanisms mediating vaginal remodeling by investigating expression and functional relevance of potential trophic factors. In aim 4, we assess the functional significance of vaginal nerve remodeling on blood flow, neurogenic inflammation and behavioral avoidance of painful stimuli. These studies are conducted using methods in cell biology, tissue culture, molecular biology, physiology, pharmacology and behavior. The findings of these experiments will provide insight into mechanisms underlying hormone-dependent remodeling of vaginal innervation, and whether altered innervation may contribute to vaginal dysfunction. Moreover, these studies will provide a better understanding of the relationship between vaginal nerve plasticity and vulvodynia, and potentially lead to new therapeuties aimed at reversing vaginal sensory hyperinnervation.