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

项目摘要 这个“职业发展奖”的目的是为Samineni博士提供一位被指导的 神经血液学研究经验，并成功地从指导性研究过渡到 作为一名神经病学家的独立调查员的职业生涯。萨米内尼博士在接下来的五年里的主要目标 多年是建立作为一名成功的独立科学家进行神经病学研究 为我们对慢性膀胱疼痛的理解提供机械性见解，并达到R01水平 资金问题。萨米内尼博士研究的长期目标是独立领导一项研究 研究缓解慢性膀胱痛的新途径并确定新的 通过进一步加深我们对慢性膀胱痛的机制的理解，提供治疗机会。至 为了实现这一目标，Samineni博士正在提出一个项目，为他提供重要的培训 神经病学。培训计划包括在博士的主要监督下严格的板凳工作。 Gereau和Andriole医生参加了以泌尿外科为重点的大查房和授课系列，介绍 在国家会议上，以及在人事管理、赠款和科学写作方面的培训。 这一培训将使Samineni医生成为一名独立的泌尿科科学家，并使他能够 在获得独立的NIH研究资助方面具有竞争力(R01)。为实现这一目标的制度环境 华盛顿大学及麻醉和泌尿系的职业发展 是不同寻常的。埃弗斯博士(麻醉科主任)承诺他将全力以赴。要实现 Samineni博士的目标是，他正在提出一个项目，通过检查 中央杏仁核(CEA)环路的非适应性可塑性如何参与IC/ Bps。具体地说，Samineni博士将研究这些回路在调节慢性疾病中的必要性和充分性。 膀胱疼痛。为了测试这一点，Samineni博士将使用光遗传技术来控制细胞的活动 并确定它们在膀胱疼痛中的相对贡献。这一建议结合了Dr。 Samineni先前利用啮齿动物在体内工作的专业知识，并推动了 遗传学、电生理学和电路解剖工具。成功完成这些研究将 确定这些回路中处理慢性膀胱疼痛和意志的适应不良机制 为开发新的治疗方法和治疗方法提供新的途径，这些方法和治疗方法将有利于 慢性膀胱痛的治疗。完成这项K01奖项将培训Samineni博士 全面、多学科的行为药理学、光遗传学和全细胞切片培训 电生理学。此外，通过K01机制进行的额外指导培训将允许Dr。 Samineni在他的训练中弥补了与运行独立的 研究计划。

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.