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

项目摘要 这个“职业发展奖”的目标是为Samineni博士提供一个有指导的 神经泌尿学研究经验，并成功地从指导研究过渡到 作为一名神经泌尿科医生的独立调查员萨米内尼博士未来五年的主要目标 多年来，作为一个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提供了机制性见解，并获得R 01水平 经费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， 通过进一步了解慢性膀胱疼痛的机制，为治疗提供机会。到 为了实现这一目标，Samineni博士提出了一个项目，为他提供了重要的培训， 神经泌尿学培训计划包括在Dr. Gereau和Andriole博士，参加泌尿外科重点大轮和教学系列，演讲 在国家会议上发言，并进行人事管理、语法和科学写作方面的培训。 这项培训将使Samineni博士成为泌尿科的独立科学家，并使他能够 在获得独立的NIH研究资助（R 01）方面具有竞争力。的制度环境 在华盛顿大学和麻醉学和泌尿学系的职业发展 是很特别的Evers博士（麻醉科主任）承诺他将全力以赴。实现 博士Samineni的目标是，他提出了一个项目，通过检查 中央杏仁核（CeA）回路中的适应不良可塑性如何导致IC中的慢性膀胱疼痛/ BPS具体来说，Samineni博士将研究这些回路在介导慢性炎症中的必要性和充分性。 膀胱疼痛。为了验证这一点，Samineni博士将使用光遗传学技术来控制细胞的活性。 CeA神经元，并确定其对膀胱疼痛的相对贡献。该提案结合了博士。 Samineni先前使用啮齿动物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的适应不良机制，并将 为开发新的疗法和治疗提供了新的途径， 治疗慢性膀胱疼痛。K 01奖的完成将培养Samineni博士， 在行为药理学、光遗传学和全细胞切片方面进行全面的多学科培训 电生理学此外，通过K 01机制进行的额外指导培训将使Dr. Samineni在他的培训中弥补了与独立运营相关技能的差距。 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.