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: 10202566
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10202566
• 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 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.

项目摘要/摘要： 该申请的受训者 Kenny Roman 博士是 Kirschstein-NRSA 的博士后研究员 西北大学泌尿外科。在奖励期间，Roman 博士将获得 实验室空间、动物饲养设施、核心实验室、设备、网络机会和关键的 优秀教师的指导，以成功完成拟议的项目。此外，该部还 泌尿外科致力于并投资于罗曼博士的未来职业生涯，并为他提供了全职研究- 跟踪教师职位。 Roman 博士的长期职业目标是 1) 提高工作效率和质量 发表基础研究，2）获得终身教职，3）生成重要的初步数据 申请有竞争力的 RO1 补助金。为了实现这些目标，罗曼博士提出了职业发展 旨在提供指导和自由之间的平衡以帮助他实现研究独立性的计划 和自我效能感。具体来说，职业发展计划包括加强他在以下领域的知识的课程： 神经科学领域，教授指导，并提升他的资助技能。 Roman博士的导师（Praveen博士） Thumbikat）和共同导师（Kevin E. McKenna 博士和 Anthony J. Schaeffer 博士）高度致力于他的研究 成功并坚信罗曼博士建立独立研究计划的潜力，获得 获得 R01 资金并管理成功的学术生涯。 拟议的项目将在 mTOR 通路的激活和改变之间建立联系 从急性向慢性转变过程中相关皮质的神经生物学和神经炎症系统 CP/CPPS 自身免疫小鼠模型（称为实验性自身免疫性前列腺炎 (EAP)）中的骨盆疼痛。 慢性盆腔疼痛多学科研究方法 (MAPP) 研究发表的最新研究 网络显示 CP/CPPS 患者的岛叶皮质受损。此外，初步数据来自 受训者的实验室表明 S6K（一种下游 mTOR 通路信号激酶）被磷酸化， 患有 EAP 的小鼠的前边缘皮质（与岛叶相连）中的 mRNA 升高。然而，细胞内 在急性期过渡期间影响特定皮质变化的信号传导机制和细胞类型 慢性盆腔疼痛的发病机制尚未得到充分探索。因此，该项目的长期目标是确定 mTOR 通路作为介导大脑中急性骨盆腔向慢性骨盆腔转变的信号机制 EAP 小鼠中神经胶质细胞相互作用引起的皮质变化。总体而言，受训者力求 1) 确定过渡 患有 EAP 的小鼠从急性骨盆疼痛到慢性骨盆疼痛，2) 确定 mTOR 通路在驱动 岛叶和前边缘皮质从急性骨盆疼痛转变为慢性骨盆疼痛，3）探索 岛叶和前边缘皮质从急性骨盆疼痛转变为慢性骨盆疼痛期间的神经炎症。 成功完成研究目标将改善治疗方案并扩大我们的研究范围 了解引发和维持 CP/CPPS 相关症状的机制。