Female Pelvic Pain, Hormones,and Neuroplasticity

女性盆腔疼痛、激素和神经可塑性

• 批准号: 7936665
• 负责人: Peter G Smith
• 金额: $ 7.3万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2010-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7936665
• 关键词: Adolescent; Adult; Animal Model; Atrophic; Autonomic ganglion; Axon; Behavior; Behavioral; Biological; Biopsy; Blood flow; Burn injury; Burning Pain; Calcitonin Gene-Related Peptide; Caliber; Cellular biology; Contraceptive Usage; Culture Media; Disease; Down-Regulation; Dryness; Estrogen Receptors; Estrogens; Estrous Cycle; Estrus; Etiology; Female; Fiber; Functional disorder; Gene Expression; Gene Proteins; Genital system; Gonadal Steroid Hormones; Health; Hormonal; Hormones; Human; Immunoblotting; In Vitro; Intervention; Juvenile Hormones; Lead; Link; Mediating; Menopausal Syndrome; Menopause; Methods; Microarray Analysis; Molecular; Molecular Biology; Nerve; Neurites; Neurogenic Inflammation; Neuronal Plasticity; Neurons; Neuropeptides; Nociceptors; Operative Surgical Procedures; Oral Contraceptives; Ovariectomy; Pain; Pelvic Pain; Peripheral Nerves; Pharmacology; Physiology; Population; Pregnancy; Proteins; Pruritus; Rattus; Response Latencies; Reverse Transcriptase Polymerase Chain Reaction; Role; Sensory; Stimulus; Syndrome; Testing; Tissues; Touch sensation; Vagina; Vascular Permeabilities; Vulva; Vulvodynia; allodynia; awake; behavior test; density; insight; nerve supply; neuromechanism; neuronal cell body; novel therapeutics; protein expression; release factor; reproductive; reproductive hormone; research study; tissue culture; vulvar vestibulitis

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.

荷尔蒙状况和阴道功能密切相关。更年期生殖激素减少 导致阴道萎缩和干燥。绝经后常伴有外阴功能障碍、疼痛。 由灼热和瘙痒组成的综合症。外阴前庭炎，一种痛觉过敏样综合征 外阴疼痛与早期口服避孕药的使用有关，它代表着一种被低估但意义重大的健康。 这一问题困扰着大约16%的美国成年女性人口。这些证候的病因很差。 可以理解，尽管外阴前庭炎与痛感纤维数量的增加有关。不是 已经有了动物模型来提供更好的理解框架。最近，我们展示了 雌激素调节大鼠的阴道神经。卵巢切除，这接近于人类更年期， 显著增加阴道伤害性感受器的数量，以及交感和副交感 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，并且 神经支配的改变将影响阴道功能的关键方面，包括血流，血管通透性， 以及疼痛敏感度。在目标1中，我们建议描述荷尔蒙状态和 大鼠发情周期、妊娠及成体和幼体激素的阴道神经支配 行政管理。我们还确定人类的阴道神经是否会随着荷尔蒙状态的变化而变化。AIM 2评估 生殖激素对轴突重塑影响的细胞机制研究 阴道靶组织以及感觉神经元和自主神经。目标3研究分子机制 通过研究潜在营养因子的表达和功能相关性来介导阴道重塑 各种因素。在目标4中，我们评估阴道神经重塑对血流的功能意义， 神经源性炎症和对疼痛刺激的行为回避。这些研究使用以下方法进行 方法细胞生物学、组织培养、分子生物学、生理学、药理学、行为学。这个 这些实验的发现将提供对激素依赖的潜在机制的洞察 阴道神经的重塑，以及神经改变是否可能导致阴道功能障碍。 此外，这些研究将提供更好的理解阴道神经之间的关系。 可塑性和外阴疼痛，并可能导致旨在逆转阴道感觉的新疗法 超神经支配。