Quantitative studies of urinary bladder sensation

膀胱感觉的定量研究

• 批准号: 7346951
• 负责人: TIMOTHY J NESS
• 金额: $ 29.13万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-25 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7346951
• 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; Condition; Cutaneous; Data; Depth; Development; Diagnosis; Disease; Distant; Elements; End Point; 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; day; dorsal horn; human study; 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(申请人提供)：源于膀胱的急性和慢性疼痛是常见的临床症状，超过50%的女性在一生中的某个时候会受到影响。有些情况很容易治疗，但另一些情况，如间质性膀胱炎(1C)，是膀胱过敏性疾病，已被证明对诊断和治疗具有抵抗力。正如最近发表的研究表明，PI使用定量感觉测试对患有1C的受试者进行了检查，发现他们对膀胱扩张和其他深层组织刺激(如肌肉压力和缺血)高度敏感。这些人类研究的PI试图以翻译的方式理解这种膀胱超敏反应，因此在啮齿类动物中，定义了脊椎和脊柱上水平的膀胱感觉的基本神经生理学要素。以UBD诱发反射为实验终点，建立了与临床相关的膀胱超敏反应模型。不幸的是，目前还不知道哪些膀胱过敏模型与1C的相关性最大。为转译研究开发模型系统的关键下一步是系统地测试这些膀胱过敏的啮齿动物模型是否与选定的疾病过程1C相似或不同。在这次竞争性更新中，PI试图通过致力于检查一种已知的改变痛感的非药理、感觉改变手法的效果，在翻译研究中迈出这一步。具体地说，该提案使用这些目的检测了异位伤害性条件性条件刺激(HNCs)对患有1C的人类感觉的影响，以及在三种机械上不同的啮齿动物膀胱超敏模型中对反射和神经元反应的影响：具体目标1：定量比较患有间质性膀胱炎(1C)的受试者与匹配对照的HNCs效应的存在和程度。具体目标#2：定量对比和比较HNCs对大鼠和小鼠膀胱过敏模型的影响，并与适当的对照组进行比较。由同一研究人员在1C人群和啮齿动物模型系统中检验HNC相关效应的拟议研究将深入了解膀胱超敏模型与病理过程的可比性，从而增加基础科学向疼痛疗法的转化。