Quantitative Studies in Urinary Bladder Sensation

（请保持文字，不要PDF） 摘要。急性和慢性疼痛起源于膀胱是常见的临床实体影响大多数女性在他们的生活中的某个时候，特别是当他们变老。在试图理解膀胱超敏反应的翻译方式，这个正在进行的研究项目已使用啮齿动物定义在脊髓和脊髓上水平的膀胱感觉的基本神经生理学元素。使用膀胱扩张（UBD）诱发的反射和初级/脊髓/脊髓上神经元反应作为实验终点，已经开发了膀胱超敏反应的临床相关模型。本申请探索了衰老对膀胱疼痛啮齿动物模型的影响，该模型利用新生儿膀胱炎症（NBI）来引起间质性膀胱炎/膀胱疼痛综合征（IC/BPS）的许多表型特征，重点是阿片样物质能和促肾上腺皮质激素释放因子受体（CRFR）相关调节机制的已知改变。提出了三个具体目标： 具体目标1：对比/比较经历新生儿膀胱炎（NBI）的大鼠及其对照组中的衰老对膀胱扩张（UBD）的反射和神经元反应以及膀胱组织学的影响。 具体目标#2：对比/比较内源性阿片系统在经历NBI的年轻成年和老年大鼠及其对照组中调节对UBD的反射和神经反应的作用。 具体目标#3：对比/比较脊髓CRF系统在经历NBI的年轻成年和老年大鼠及其对照组中调节反射和神经元对UBD的反应的作用。 在啮齿动物模型系统中进行的拟议研究将提供与膀胱感觉相关的见解，以及在探索新疗法的同时如何通过衰老改变膀胱感觉。对膀胱感觉通路相关感觉处理及其二次损伤调制的更好理解将导致基础科学向膀胱疼痛治疗学的转化增加。

(PLEASE KEEP IN WORD, DO NOT PDF) ABSTRACT. Acute and chronic pains originating from the urinary bladder are common clinical entities affecting most females at some time in their lives, particularly as they get older. In an attempt to understand urinary bladder hypersensitivity in a translational manner, this ongoing research project has used rodents to define basic neurophysiological elements of bladder sensation at spinal and supraspinal levels. Using urinary bladder distension (UBD)-evoked reflexes and primary/spinal/supraspinal neuronal responses as experimental endpoints, clinically relevant models of bladder hypersensitivity have been developed. The present application explores the effect of aging on a rodent model of bladder pain that utilized neonatal bladder inflammation (NBI) to evoke many of the phenotypic features of interstitial cystitis/bladder pain syndrome (IC/BPS) with an emphasis on known alterations in opioidergic and corticotrophin releasing factor receptor (CRFR)-related modulatory mechanisms. Three Specific Aims are proposed: Specific Aim #1: To contrast/compare the effect of aging in rats which experienced neonatal bladder inflammation (NBI) and their controls on reflex and neuronal responses to urinary bladder distension (UBD) and bladder histology. Specific Aim #2: To contrast/compare the role of endogenous opioid systems modulating reflex & neuronal responses to UBD in both young adult and aged rats which experienced NBI and their controls. Specific Aim #3: To contrast/compare the role of spinal CRF systems modulating reflex & neuronal responses to UBD in both young adult and aged rats which experienced NBI and their controls. The proposed studies in rodent model systems will give insight related to bladder sensation and how it is altered by aging while exploring novel therapeutics. An improved understanding of sensory processing related to urinary bladder sensory pathways and their modulation by secondary insults will result in an increased translation of basic science to therapeutics for bladder pain.