DEFINING THE NEURAL BASIS FOR CHRONIC BLADDER PAIN AND ITS ASSOCIATED COMORBID DISORDERS

定义慢性膀胱疼痛及其相关合并症的神经基础

• 批准号: 9750743
• 负责人: Vijay K Samineni
• 金额: $ 11.62万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9750743
• 关键词: Address; Affect; Affective; Amygdaloid structure; Anatomy; Anesthesiology; Anxiety; Applications Grants; Behavior; Bladder; Bladder Diseases; Brain; Brain region; Cells; Chronic; Clinical; Comorbidity; Cystitis; Development; Disease; Dissection; Electrophysiology (science); Environment; Etiology; Funding; Future; Genetic; Goals; Halorhodopsins; Interstitial Cystitis; K-Series Research Career Programs; Lead; Left; Light; Local Therapy; Maintenance; Mediating; Mental Depression; Mentored Research Scientist Development Award; Mentors; Mood Disorders; Neuraxis; Neurons; Nociception; Pathology; Patients; Pelvic Pain; Peripheral; Personnel Management; Population; Process; Pump; Research; Research Personnel; Research Project Grants; Research Proposals; Rodent; Role; Running; Scientist; Series; Slice; Stimulus; Supervision; Symptoms; Synapses; Synaptic Transmission; Syndrome; System; Techniques; Testing; Training; United States; United States National Institutes of Health; Universities; Urology; Washington; Woman; Work; Writing; afferent nerve; anatomical tracing; base; behavioral pharmacology; bladder pain; career; career development; cell type; central sensitization; chronic neuropathic pain; chronic pain; experience; experimental study; in vivo; inflammatory pain; innovation; insight; meetings; mouse model; multidisciplinary; negative affect; neural circuit; neuromechanism; neuronal circuitry; novel therapeutics; optogenetics; pain behavior; programs; psychosocial; recruit; relating to nervous system; selective expression; skills; skills training; therapeutic target; tool

Project Summary The goal of this “Career Development Award” is to provide Dr. Samineni with a mentored neurourology research experience and to successfully bridge transition from mentored research to a career as an independent investigator as a neurourologist. Dr. Samineni’s primary goal in the next five years is to establish as a successful independent scientist conducting neurourology research that provides mechanistic insights into our understanding of chronic bladder pain and to obtain R01 level funding. The long-term goal of Dr. Samineni’s research is to independently lead a research group that investigates new avenues for relief of chronic bladder pain and identify new therapeutic opportunities through furthering our mechanistic understanding of chronic bladder pain. To achieve this goal, Dr. Samineni is proposing a project that provides him with significant training in neurourology. Training plan includes rigorous bench work under the primary supervision of Dr. Gereau and Dr. Andriole, attending urology focused grand rounds and didactic series, presentations at national meetings, and training in personnel management, grantsmanship and scientific writing. This training will enable Dr. Samineni to become an independent scientist in urology and allow him to be competitive in obtaining an independent NIH research grant (R01). The institutional environment for career development at Washington University and in the Department of Anesthesiology and Urology is exceptional. Dr. Evers (Chief of Anesthesiology) pledged his full department commitment. To achieve Dr. Samineni’s goal, he is proposing a project that provides him with significant training by examining how maladaptive plasticity in the central amygdala (CeA) circuit contributes to chronic bladder pain in IC/ BPS. Specifically, Dr. Samineni will examine necessity and sufficiency of these circuits in mediating chronic bladder pain. To test this, Dr. Samineni will use optogenetic techniques to control the activity of the CeA neurons and determine their relative contribution to bladder pain. This proposal combines Dr. Samineni’s prior expertise using rodent in vivo work, and pushes forward an innovative combination of genetics, electrophysiology and circuit dissecting tools. Successful completion of these studies will identify the maladaptive mechanisms in these circuits for processing chronic bladder pain and will provide new avenues for developing novel therapies and treatments that would be beneficial for the treatment of chronic bladder pain. Completion of this K01 award will train Dr. Samineni with comprehensive, multidisciplinary training in behavioral pharmacology, optogenetics and whole-cell slice electrophysiology. Furthermore, additional mentored training via the K01 mechanism will allow Dr. Samineni to bridge the gap in his training with regard to skills relevant to running an independent research program.

项目概要 该“职业发展奖”的目标是为 Samineni 博士提供指导 神经泌尿学研究经验，并成功地将指导研究过渡到 作为神经泌尿科医生的独立调查员的职业生涯。 Samineni 博士未来五年的主要目标 年是成为一名成功的独立科学家，进行神经泌尿学研究 为我们理解慢性膀胱疼痛并获得 R01 水平提供机制见解 资金。 Samineni博士研究的长期目标是独立领导一项研究 该小组研究缓解慢性膀胱疼痛的新途径并确定新的方法 通过进一步了解慢性膀胱疼痛的机制来获得治疗机会。到 为了实现这一目标，Samineni 博士提出了一个项目，为他提供以下方面的重要培训： 神经泌尿学。培训计划包括在博士的主要监督下进行严格的工作台工作。 Gereau 和 Andriole 博士参加以泌尿科为重点的大型查房和教学系列、演讲 国家会议以及人事管理、资助和科学写作方面的培训。 此次培训将使 Samineni 博士成为泌尿科的独立科学家，并让他能够 在获得独立的 NIH 研究补助金 (R01) 方面具有竞争力。的制度环境 华盛顿大学以及麻醉科和泌尿科的职业发展 是例外。 Evers 博士（麻醉科主任）承诺全力投入科室工作。达到 Samineni 博士的目标是提出一个项目，通过检查为他提供重要的培训 中央杏仁核 (CeA) 回路的适应不良可塑性如何导致 IC/慢性膀胱疼痛 BPS。具体来说，Samineni 博士将检查这些回路在调节慢性疾病方面的必要性和充分性。 膀胱疼痛。为了测试这一点，Samineni 博士将使用光遗传学技术来控制 CeA 神经元并确定它们对膀胱疼痛的相对贡献。该提案结合了博士。 Samineni 先前在啮齿动物体内工作方面的专业知识，并推动了创新组合 遗传学、电生理学和电路剖析工具。成功完成这些研究将 确定这些处理慢性膀胱疼痛的回路中的适应不良机制，并将 为开发新疗法和治疗方法提供新途径，这将有利于人类 治疗慢性膀胱疼痛。完成 K01 奖项将为 Samineni 博士提供以下培训： 行为药理学、光遗传学和全细胞切片方面的全面、多学科培训 电生理学。此外，通过 K01 机制进行的额外指导培训将使 Dr. 萨米尼将弥补他在经营独立公司相关技能方面的培训差距 研究计划。