Transition from Acute to Chronic Pelvic Pain in a Murine Model of Chronic Prostatitis

慢性前列腺炎小鼠模型中从急性盆腔疼痛到慢性盆腔疼痛的转变

• 批准号: 10440303
• 负责人: Kenny M Roman
• 金额: $ 10.9万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-11 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10440303
• 关键词: Acute; Address; Animal Housing; Animal Model; Anogenital region; Anxiety; Astrocytes; Autoimmune; Automobile Driving; Autophagocytosis; Award; Basic Science; Behavioral Assay; Brain; Brain region; Calcium; Chronic; Chronic Prostatitis; Complex; Cyclin-Dependent Kinase 5; Data; Development; Development Plans; Equilibrium; Etiology; FRAP1 gene; Faculty; Freedom; Functional Magnetic Resonance Imaging; Funding; Future; Genital; Genitalia; Goals; Grant; Hippocampus (Brain); Human; Hyperalgesia; Image; Immunohistochemistry; Impairment; Increased frequency of micturition; Inflammatory; Insula of Reil; Knowledge; Laboratories; Lesion; Link; Mediating; Mentors; Mentorship; Metabolism; Microglia; Mus; National Research Service Awards; Neuraxis; Neurobiology; Neuroglia; Neurons; Neurosciences; Pain; Pain Disorder; Pathogenesis; Pathway interactions; Patients; Pelvis; Phosphorylation; Phosphotransferases; Play; Population Control; Positioning Attribute; Postdoctoral Fellow; Productivity; Prostate; Protein Biosynthesis; Publishing; Quality of life; Quantitative Reverse Transcriptase PCR; Rattus; Reporting; Research; Rodent; Role; Sacral spinal cord structure; Self Efficacy; Sensory; Signal Pathway; Signal Transduction; Sirolimus; Symptoms; Synaptic plasticity; System; Time; Universities; Urethra; Urology; Visceral pain; associated symptom; base; career; career development; cell type; chronic pain; chronic pelvic pain; cohort; design; excitatory neuron; experience; functional MRI scan; improved; interdisciplinary approach; interest; laboratory equipment; men; mouse model; neuroinflammation; neuron development; new therapeutic target; pain chronification; pain model; programs; prostatitis; reduce symptoms; response; skills; success; tenure track; therapeutic target; transcription factor; urinary

Project Summary/Abstract: The mentee of the application, Dr. Kenny Roman, is a Kirschstein-NRSA postdoctoral fellow in the Department of Urology at Northwestern University. During the award period, Dr. Roman will be provided with laboratory space, animal housing facilities, core labs, equipment, networking opportunities, and crucial mentorship from accomplished faculty to successfully complete the proposed project. Also, the Department of Urology is committed and invested in the future career of Dr. Roman and has offered him a full-time research- track faculty position. Dr. Roman's long term career goals are to 1) to increase his productivity and quality of published basic research, 2) obtain a tenured-track faculty position, and 3) generate significant preliminary data to apply for a competitive RO1 grant. To achieve these goals, Dr. Roman has proposed a career development plan that's designed to provide a balance of mentorship and freedom to help him achieve research independence and self-efficacy. Specifically, the career development plan includes courses to strengthen his knowledge in the field of neuroscience, teach mentorship, and promote his grantsmanship skills. Dr. Roman's mentor (Dr. Praveen Thumbikat) and co-mentors (Dr. Kevin E. McKenna and Dr. Anthony J. Schaeffer) are highly committed to his success and strongly believe in Dr. Roman's potential to establish an independent research program, attain the expertise to obtain R01 funds, and manage a successful academic career. The proposed project will establish a link between activation of the mTOR pathway and changes to neurobiological and neuroinflammatory systems in relevant cortices during the transition from acute to chronic pelvic pain in an autoimmune mouse model of CP/CPPS called experimental autoimmune prostatitis (EAP). Recent studies published by the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) research network showed that the insular cortex is impaired in patients with CP/CPPS. Moreover, preliminary data from the mentee's laboratory suggests the phosphorylation of S6K, a downstream mTOR pathway signaling kinase, is elevated in the prelimbic cortex (interconnected to the insula) of mice with EAP. However, the intracellular signaling mechanisms and cell types that influence changes in specific cortices during the transition from acute to chronic pelvic pain have not been fully explored. Therefore, the long term goal of this project is to identify the mTOR pathway as a signaling mechanism that mediates the transition from acute to chronic pelvic in brain cortices due to neuro-glia interactions in mice with EAP. Overall, the mentee seeks to 1) determine the transition from acute to chronic pelvic pain in mice with EAP, 2) establish the role of the mTOR pathway in driving the transition from acute to chronic pelvic pain in insular and prelimbic cortices, and 3) explore the contribution of neuroinflammation during the transition from acute to chronic pelvic pain in the insular and prelimbic cortices. Successful completion of the research aims will lead to improved treatment options and expand our understanding of the mechanisms that initiate and maintain symptoms associated with CP/CPPS.

项目概要/摘要： Kenny Roman博士是Kirschstein-NRSA博士后研究员， 西北大学泌尿外科。在奖励期间，罗曼博士将获得 实验室空间、动物饲养设施、核心实验室、设备、网络机会，以及关键的 从成功的教师指导，以成功地完成拟议的项目。此外， 泌尿科致力于罗曼博士未来的职业生涯，并为他提供了一个全职的研究- 跟踪教师的位置。罗曼博士的长期职业目标是：1）提高他的生产力和质量， 发表的基础研究，2）获得终身教职，3）产生重要的初步数据 申请竞争性RO 1补助金。为了实现这些目标，罗曼博士提出了一个职业发展 该计划旨在提供指导和自由的平衡，以帮助他实现研究独立 和自我效能。具体而言，职业发展计划包括课程，以加强他在 神经科学领域，教授导师制，提升他的专业技能。Roman博士的导师（Praveen博士 Thumbikat）和共同导师（Kevin E. McKenna和Anthony J. Schaeffer博士）高度致力于 成功，并坚信罗曼博士的潜力，建立一个独立的研究计划，实现 获得R 01资金并管理成功的学术生涯的专业知识。 拟议的项目将建立mTOR通路的激活与以下变化之间的联系： 从急性向慢性过渡期间相关皮质中的神经生物学和神经炎症系统 在称为实验性自身免疫性前列腺炎（EAP）的CP/CPPS的自身免疫小鼠模型中的骨盆疼痛。 慢性盆腔疼痛研究的多学科方法（MAPP）研究 网络显示，CP/CPPS患者的岛叶皮质受损。此外，来自 学员的实验室表明S6 K（一种下游mTOR途径信号激酶）的磷酸化， 在患有EAP的小鼠的前边缘皮层（与大脑皮层互连）中升高。然而，细胞内 信号传导机制和细胞类型，影响从急性 慢性盆腔疼痛的病因尚未得到充分研究。因此，本项目的长期目标是确定 mTOR通路作为介导脑内急性盆腔炎向慢性盆腔炎转变的信号机制 在患有EAP的小鼠中由于神经胶质相互作用而导致的皮质损伤。总体而言，学员寻求1）确定过渡 从急性到慢性盆腔疼痛的EAP小鼠，2）建立mTOR通路在驱动 岛叶和前边缘皮质从急性骨盆疼痛向慢性骨盆疼痛的转变，以及3）探索 神经炎症从急性过渡到慢性盆腔疼痛在岛叶和前边缘皮质。 研究目标的成功完成将改善治疗方案，扩大我们的 了解启动和维持与CP/CPPS相关症状的机制。