SENSORY AND SYMPATHETIC EFFECTS ON INTERSTITIAL CYSTITIS

描述（改编自申请人的摘要）： 这项研究是为了确定感觉和交感肢的作用 间质性膀胱炎（IC）的病理生理学的神经系统。 IC是一种疼痛性、炎症性膀胱疾病。 症状 IC（疼痛和尿频和尿急增加）可能会加剧 压力的经验。 原因不明。 显著 在理解IC的过程中，一直缺乏动物 疾病的模型。 使用NIDDK授予DK 47537，校长 研究人员表明，大多数猫提交给兽医， 满足所有客观标准， 可以应用于动物的人类IC诊断。 而且 两者的自然史和病理生理特征相似 物种，使IC在猫一个很好的自发性疾病 模型 这个为期四年的提案旨在使用带有IC的猫来实现 以下目的：1）确定是否抑制感觉传入 神经元与辣椒素，或交感神经传出神经元与 6-羟基多巴胺，允许解决临床，膀胱， IC中存在传入、中枢和传出神经系统异常; 2)确定IC和药物给药对体外 膀胱条收缩性;和3）确定长期（6个月） 导致膀胱最大分辨率的药物效果 异常 这些药物的临床效果与 它们对膀胱和神经系统的影响应该提供重要的新的 对许多观察到的异常的机制的见解， IC患者，并建议更合理的治疗方法， 比目前的疾病。

DESCRIPTION (Adapted from the Applicant's Abstract): The long-term goal of this research is to determine the role of the sensory and sympathetic limbs of the nervous system on the pathophysiology of interstitial cystitis (IC). IC is a painful, inflammatory bladder disease of human beings. The symptoms of IC (pain and increased urinary frequency and urgency) may be exacerbated by stressful experience. The cause(s) is (are) unknown. A significant impediment to progress in understanding IC has been the lack of an animal model of the disease. Using NIDDK grant DK 47537, the principal investigator has shown that the majority of cats presented to veterinarians for care of irritative voiding meet all of the objective criteria for diagnosis of IC in humans that can be applied to animals. Moreover, the natural history and pathophysiologic features are comparable in both species, making IC in cats an excellent spontaneously occurring disease model. This four year proposal is intended to use cats with IC to achieve the following objectives: 1) to determine if inhibiting sensory afferent neurons with capsaicin, or sympathetic efferent neurons with 6-hydroxydopamine, permits resolution of the clinical, bladder, and afferent, central and efferent nervous system abnormalities present in IC; 2) to determine the effects of IC and drug administration on in-vitro bladder strip contractility; and 3) to determine the long-term (6 month) effects of the drug that results in the greatest resolution of bladder abnormalities. The correlation of the clinical effects of these drugs with their effects on the bladder and nervous system should provide important new insights on the mechanisms underlying many of the abnormalities observed in patients with IC, and suggest more rational approaches to treatment of the disease than currently are available.