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: 10669374
• 负责人: Kenny M Roman
• 金额: $ 5.46万
• 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/10669374
• 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.

项目摘要/摘要： 该申请的导师肯尼·罗曼博士是科尔施斯坦-NRSA大学的博士后研究员。 西北大学泌尿外科。在颁奖期间，罗曼博士将获得 实验室空间、动物收容所设施、核心实验室、设备、网络机会以及至关重要的 来自有成就的教员的指导，以成功地完成提议的项目。此外，美国国务院 泌尿科致力于并投资于罗曼博士未来的职业生涯，并为他提供了一项全职研究- 跟踪教职员工的位置。罗曼博士的长期职业目标是：1)提高他的工作效率和质量 发表基础研究，2)获得终身教职，3)产生重要的初步数据 申请竞争性RO1奖助金。为了实现这些目标，罗曼博士提出了职业发展的建议 该计划旨在提供指导和自由之间的平衡，以帮助他实现研究独立 和自我效能感。具体地说，职业发展计划包括课程，以加强他在 在神经科学领域，教授导师，并提升他的天赋技能。罗曼博士的导师(普拉文博士 Thumbikat)和共同导师(Kevin E.McKenna博士和Anthony J.Schaeffer博士)高度致力于他的 成功并坚信罗曼博士有潜力建立一个独立的研究计划，实现 专业知识，以获得R01资金，并管理成功的学术生涯。 拟议的项目将在激活mTOR途径和改变 急性向慢性转变过程中相关皮质的神经生物学和神经炎性系统 一种称为实验性自身免疫性前列腺炎(EAP)的CP/CPPS自身免疫性小鼠模型的盆腔疼痛。 多学科研究慢性盆腔疼痛(MAPP)研究发表的最新研究 网络研究显示，CP/CPPS患者的岛叶皮质受损。此外，来自 受训者的实验室表明，下游的mTOR信号通路激酶S6K发生了磷酸化， 在EAP小鼠的大脑皮层(与脑岛相连)中升高。然而，细胞内的 信号机制和细胞类型，影响特定皮质在从急性转变期间的变化 对慢性盆腔疼痛尚未有充分的认识。因此，这个项目的长期目标是确定 MTOR通路作为脑内骨盆急慢性转变的信号机制 EAP小鼠神经胶质细胞相互作用所致的大脑皮层。总的来说，被辅导者寻求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 在岛叶和前皮质从急性到慢性骨盆疼痛的过渡，以及3)探讨 在从急性到慢性盆腔疼痛的过渡过程中，岛叶和前皮质的神经炎症。 成功完成研究目标将带来更好的治疗选择并扩大我们的 了解引发和维持CP/CPPS相关症状的机制。

项目成果

Translational research updates in female health anesthesiology: a narrative review.

• DOI: 10.21037/atm-22-3547
• 发表时间: 2023-08-30
• 期刊: ANNALS OF TRANSLATIONAL MEDICINE
• 作者: Ibarra, Andrea J;Roman, Kenny;Nguyen, Eileen;Yates, Megan E;Nicholas, Alexandra;Lim, Grace
• 通讯作者: Lim, Grace