Quantitative studies of urinary bladder sensation

膀胱感觉的定量研究

• 批准号: 7854827
• 负责人: TIMOTHY J NESS
• 金额: $ 1.67万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-16 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7854827
• 关键词: Acute; Address; Adult; Affect; Age; Anxiety; Basic Science; Biological Models; Bladder; Body part; Brain Stem; Cell Wall; Characteristics; Chronic; Chronic stress; Clinical; Cutaneous; Data; Development; Diagnosis; Disease; Distant; Elements; Esthesia; Female; Fibromyalgia; Frequencies; General Population; Generations; Hand; Health; Human; Hypersensitivity; Ice; Immersion Investigative Technique; Inflammation; Inflammatory; Interstitial Cystitis; Intravesical Administration; Irritable Bowel Syndrome; Ischemia; Life; Measures; Modeling; Mus; Muscle; Neonatal; Neurons; Pain; Pathologic Processes; Pathway interactions; Patients; Perception; Population; Posterior Horn Cells; Principal Investigator; Process; Publishing; Questionnaires; Rattus; Reflex action; Research Personnel; Research Support; Resistance; Rheumatoid Arthritis; Rodent; Rodent Model; Secondary to; Sensory; Sensory Process; Spinal; Stimulus; Stress; System; Temporomandibular Joint Disorders; Tension Headache; Testing; Therapeutic; Time; Tissues; Translational Research; Translations; Water; Yeasts; Zymosan; base; chronic pain; clinically relevant; conditioning; dorsal horn; human subject; improved; insight; neonate; neurophysiology; pressure; programs; response; sex

DESCRIPTION (provided by applicant): Acute and chronic pains originating from the urinary bladder are common clinical entities affecting more than 50% of females at some time in their lives. Some conditions are easy to treat, but others, such as interstitial cystitis (1C), are conditions of bladder hypersensitivity that have proven resistant to diagnosis and treatment. As demonstrated in recently published studies, the PI has examined subjects with 1C using quantitative sensory testing and found them to be hypersensitive to bladder distension and other deep tissue stimuli such as muscle pressure and ischemia. The PI of these human studies has sought to understand this urinary bladder hypersensitivity in a translational manner and so in rodents has defined basic neurophysiological elements of bladder sensation at spinal and supraspinal levels. Using UBD-evoked reflexes as experimental endpoints, clinically-relevant models of bladder hypersensitivity were developed. Unfortunately, it is not known which models of bladder hypersensitivity have the greatest relevance to 1C. A critical next step in the development of model systems for translational research is to systematically test these rodent models of bladder hypersensitivity for similarity or dissimilarity to the selected disease process, 1C. In this competitive renewal the PI seeks to take this next step in translational research by concommitantly examining the effects of a non-pharmacologic, sensation-modifying manipulation known to alter the sensation of pain. Specifically, the proposal examines the effect of Heterotopic Noxious Conditioning Stimulus (HNCS) administration on sensations of humans with 1C and on reflex and neuronal responses in three mechanistically-different, rodent bladder hypersensitivity modelSi using these Aims: Specific Aim #1: To quantitatively compare the presence and magnitude of HNCS effects in human subjects with interstitial cystitis (1C) with matched controls. Specific Aim #2: To quantitatively contrast and compare the magnitude of HNCS effects in rat and murine models of bladder hypersensitivity with appropriate controls. The proposed studies examining HNCS-related effects in the 1C population and in rodent model systems by the same researcher will give insight into the comparability of models of bladder hypersensitivity with pathological processes and thereby increase the translation of basic science to therapeutics for pain.

描述（由申请人提供）：源自膀胱的急性和慢性疼痛是常见的临床实体，影响超过50%的女性在其生命中的某个时间。有些情况很容易治疗，但其他情况，如间质性膀胱炎（1C），是膀胱超敏反应的条件，已被证明耐诊断和治疗。如最近发表的研究所示，PI使用定量感觉测试检查了1C受试者，发现他们对膀胱扩张和其他深部组织刺激（如肌肉压力和缺血）过敏。这些人体研究的PI试图以翻译方式理解这种膀胱超敏反应，因此在啮齿动物中定义了脊髓和脊髓上水平膀胱感觉的基本神经生理学要素。使用UBD诱发的反射作为实验终点，开发了膀胱超敏反应的临床相关模型。不幸的是，目前还不知道哪些膀胱超敏反应模型与1C的相关性最大。转化研究模型系统开发的关键下一步是系统地测试这些啮齿动物膀胱超敏反应模型与所选疾病过程1C的相似性或不相似性。在本次竞争性更新中，PI试图通过共同检查已知可改变疼痛感觉的非药理学、感觉修饰操作的影响，在转化研究中迈出下一步。具体而言，该提案使用以下目的检查了异位伤害性条件刺激（HNCS）给药对患有IC的人类感觉以及对三种机械不同的啮齿动物膀胱超敏反应模型Si中的反射和神经元反应的影响：具体目的#1：定量比较HNCS效应在患有间质性膀胱炎（IC）的人类受试者与匹配对照中的存在和程度。具体目标#2：定量对比和比较HNCS在大鼠和小鼠膀胱超敏反应模型中与适当对照的作用程度。由同一研究人员在1C人群和啮齿动物模型系统中检查HNCS相关影响的拟议研究将深入了解膀胱超敏反应模型与病理过程的可比性，从而增加基础科学向疼痛治疗的转化。