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; 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： 该应用程序的受训者肯尼·罗曼（Kenny Roman）是Kirschstein-nrsa博士后研究员 西北大学泌尿外科系。在颁奖期间，将为罗马博士提供 实验室空间，动物住房设施，核心实验室，设备，网络机会和关键 从成就的教师到成功完成拟议项目的指导。另外，部门 泌尿科是在罗曼博士的未来职业上投入的，并为他提供了一项全日制研究 - 跟踪教师职位。罗曼博士的长期职业目标是1）提高他的生产力和质量 已发表的基础研究，2）获得终身轨道职位，3）产生重要的初步数据 申请有竞争力的RO1赠款。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平衡的计划，以帮助他实现研究独立性 和自我效能。具体而言，职业发展计划包括加强他在 神经科学领域，教导指导并促进他的授予技巧。罗曼博士的导师（普雷文博士 Thumbikat）和联合给予者（Kevin E. McKenna博士和Anthony J. Schaeffer博士）非常致力于他的 成功并坚信罗曼博士建立独立研究计划的潜力，达到 获得R01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途径激活与更改为 从急性到慢性的过渡期间，相关皮质的神经生物学和神经炎症系统 CP/CPP的自身免疫小鼠模型中的骨盆疼痛，称为实验性自身免疫性前列腺炎（EAP）。 慢性骨盆疼痛研究（MAPP）研究的多学科方法发表的最新研究 网络表明，CP/CPP患者的岛状皮质受损。此外，来自 受训者的实验室建议S6K的磷酸化，S6K是一种下游MTOR途径信号激酶， 在与EAP的小鼠的前比皮层（与绝缘体互连）中升高。但是，细胞内 在急性过渡期间影响特定皮质变化的信号传导机制和细胞类型 尚未完全探索慢性骨盆疼痛。因此，该项目的长期目标是确定 MTOR途径是一种信号传导机制，它介导了大脑中急性到慢性骨盆的过渡 与EAP小鼠中神经 - 胶质相互作用引起的皮质。总体而言，指导者寻求1）确定过渡 从EAP的小鼠中，从急性到慢性骨盆疼痛，2）确定MTOR途径在驱动驱动中的作用 在岛状和前皮层中从急性到慢性骨盆疼痛的过渡，以及3）探索的贡献 在岛状和前皮层的慢性骨盆疼痛的过渡过程中，神经炎症。 成功完成研究目标将导致改善治疗方案，并扩大我们的 了解引发和维持与CP/CPP相关的症状的机制。