Brain Bladder Interactions in IC/PBS

IC/PBS 中脑膀胱的相互作用

• 批准号: 7935534
• 负责人: Emeran A Mayer
• 金额: $ 20.02万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-27 至 2011-09-26
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7935534
• 关键词: Brain; Bladder; Interactions; IC; PBS

DESCRIPTION, OVERALL (provided by applicant): Interstitial cystitis/painful bladder syndrome (IC/PBS) is a common chronic bladder syndrome characterized by bladder pain and discomfort (urgency) and increased frequency of urination. It is part of a larger group of chronic functional pain disorders, which also include such common disorders as irritable bowel syndrome (IBS) and fibromyalgia (FM). A common feature of these syndromes is that they are multifactorial and present clinically as a mosaic of biologic and psychologic phenotypes. Despite intense, largely target organ-based drug development efforts, existing treatments are unsatisfactory. The current proposal, co-directed by experienced, senior investigators from gastroenterology and urology builds on this interdisciplinary view and aims to characterize the interactions of biological and environmental vulnerability factors to shape behavioral and neurobiological endophenotypes, and ultimately clinical phenotypes in IC/PBS. The 3 Projects of the proposal address the following 3 areas: Project 1 is a targeted epidemiological project studying the impact of genetic markers, early life experiences and adult stress on IC/PBS symptoms and comorbid pain syndromes. Project 2 is a clinical/translational study in a small cohort of IC/PBS patients (and in a rodent model of early life and chronic stress) which aims at characterizing several neurobiological and behavioral endophenotypes, and identifying their relationship to gene polymorphisms. Project 3 is a basic science study in IC/PBS patients and in the same rodent stress model which aims at studying cellular and molecular consequences of altered noradrenergic/SNS signaling on the urothelium and spinal glial cells. These projects involve a wide range of epidemiological, psychophysiological, neurobiological and molecular techniques, performed by an interdisciplinary group of investigators ranging from Urology, Gastroenterology, Epidemiology and Neuroscience, who have access to an established infrastructure to study neurovisceral interactions, and who have extensive previous experience in the study of functional pain syndromes, including IBS and IC/PBS. The projects closely interact with each other, and project investigators have been interacting with a large group of researchers and affiliated institutions. By deconstructing the complex, symptom-based syndrome of IC/PBS into distinct, neurobiological and behavioral endophenotypes, we anticipate the identification of more rationale drug development targets, and ultimately the development of more effective therapies.

描述，总体（由申请人提供）：间质性膀胱炎/疼痛膀胱综合征（IC/PBS）是一种常见的慢性膀胱综合征，其特征是膀胱疼痛和不适（紧急）（紧急）和排尿频率增加。它是一组较大的慢性功能性疼痛障碍的一部分，其中还包括诸如肠易激综合征（IBS）和纤维肌痛（FM）之类的常见疾病。这些综合症的一个共同特征是它们是多因素的，并且在临床上是生物学和心理学表型的镶嵌物。尽管强烈，主要是基于器官的药物开发工作，但现有的治疗却不令人满意。由经验丰富的胃肠病学和泌尿外科的高级研究人员共同指导的当前提案以这种跨学科观点为基础，旨在表征生物和环境脆弱性因素的相互作用，以塑造IC/PBS中最终的临床表型，以塑造行为和神经生物学内生物学型。该提案的3个项目涉及以下3个领域：项目1是一个有针对性的流行病学项目，研究了遗传标记，早期生活经历和成人压力对IC/PBS症状和合并症疼痛综合征的影响。项目2是一小部分IC/PBS患者（以及早期生命和慢性压力的啮齿动物模型）中的一项临床/转化研究，旨在表征几种神经生物学和行为内表型，并确定其与基因多态性的关系。项目3是IC/PBS患者和相同啮齿动物应力模型中的一项基础科学研究，旨在研究尿路上皮和脊柱神经胶质细胞上的甲肾上腺素能/SNS信号改变的细胞和分子后果。这些项目涉及一系列流行病学，心理生理，神经生物学和分子技术，由跨学科研究人员组成的研究人员从泌尿外科，胃肠病学，流行病学和神经科学范围内进行，这些研究人员能够使用既定的基础结构，这些基础设施都可以研究神经循环范围，并研究了与先前的ISSCERAL INTERACTOR综合体验，并具有涉及的经验，并在研究中进行了研究。 IC/PBS。这些项目彼此紧密互动，项目调查人员一直在与大量的研究人员和附属机构进行互动。通过将IC/PBS基于症状的基于症状的综合征解构为不同的，神经生物学和行为内表型，我们预计可以鉴定出更多的理由药物开发靶标，并最终鉴定出更有效的疗法。