Chicago Center on Musculoskeletal Pain (C-COMP) (Overall Application)

项目总结 我们寻求建立一个新的以资源为基础的中心，以促进和支持旨在 了解与肌肉骨骼(MSK)和风湿疾病相关的疼痛的潜在机制， 最终目标是更好地管理和预防它。世界上三分之一的人口受到 慢性疼痛，而MSK系统是最普遍的疼痛和残疾的来源。目前可用 止痛药对有限数量的目标起作用，它们不能提供持续的疼痛缓解和慢性疼痛 使用会产生严重的不良反应。确定安全和有效的主要障碍之一 产生止痛的药物是我们普遍缺乏对MSK疼痛潜在机制的了解，以及 这些机制在不同类型的风湿性疾病和MSK疾病之间可能有何重叠或不同。这个 芝加哥肌肉骨骼疼痛中心(C-COMP)将以及时和独特的方式满足这一需求， 利用我们在MSK研究、疼痛和治疗领域可用的世界级专业知识 神经生物学以实现以下广泛的长期目标：(1)整合基础、翻译和临床 多学科中心的专业知识，将为推广MSK Pain提供领导和资源 研究；(2)改善MSK研究社区的研究环境，提供 用于研究疼痛的世界级专业知识和最先进的资源、技术和基础设施； 促进MSK研究领域与疼痛/神经科学领域之间的跨学科研究；(4) 通过吸引早期职业和知名研究人员来扩大MSK Pain研究社区 研究领域。我们设想有三个核心运行，以支持这些总体目标。行政核心A (PI：A.M.Malfait；联合导演：J.J.雅各布斯)将提供领导，保持有效沟通，与 相关中心鼓励人工翻译调查结果，并实施动态丰富计划。这个 行为资源核心B(PI：R.E.Miller；联席主任：D.R.Sumner)将提供集中资源 促进各种风湿性和MSK疾病动物模型的行为分析，包括培训 对于行为测试，访问定制的协议、设备和空间以执行测试，咨询 服务和针对行为测试的定制、全方位服务选项。神经生物学核心C(PI：RJ Miller； 导演：D.R.Sumner)将提供最先进的技术来评估和操纵神经元电路 涉及疼痛生理学，如体内钙成像、电生理学、化学/光遗传学、 转录学/生物信息学和神经解剖学技术。这将使该中心的研究社区 致力于MSK病动物模型疼痛机制的前沿研究。在……里面 总而言之，C-Comp将提供(1)独特的资源和基础设施，用于外部支持高质量 资助研究和(2)以多学科和协作的方式试点资助、教育和培训。 这一综合方法有望加快与MSK和风湿病相关的疼痛研究。

Project summary We seek to establish a new resource-based Center to foster and support research and training aimed at understanding the mechanisms underlying pain associated with musculoskeletal (MSK) and rheumatic diseases, with the ultimate goal of better managing and preventing it. One third of the world’s population is affected by chronic pain, and the MSK system is the most prevalent source of pain and disability. Currently available analgesic drugs act on a limited number of targets, and they do not provide sustained pain relief and their chronic use is associated with serious adverse effects. One of the major obstacles in identifying safe and efficacious drugs for producing pain relief is our general lack of understanding of the mechanisms underlying MSK pain, and how these mechanisms may overlap or differ between different types of rheumatic and MSK diseases. The Chicago Center on Musculoskeletal Pain (C-COMP) will address this need in a timely and unique manner, capitalizing on the world class expertise that is available to us in the areas of MSK research, pain and neurobiology to achieve the following broad long-term goals: (1) To integrate basic, translational and clinical expertise in a multidisciplinary Center which will provide the leadership and resources for promoting MSK pain research; (2) To enhance the research environment for the MSK research community by providing access to world-class expertise and state-of-the-art resources, technologies, and infrastructure for studying pain; (3) To promote interdisciplinary research between the MSK research field and the field of pain/neuroscience; (4) To expand the MSK pain research community by attracting early career as well as established researchers into this area of study. We envision three Cores operating in support of these overall goals. The Administrative Core A (PI: A.M. Malfait; co-director: J.J. Jacobs) will provide leadership, maintain effective communication, partner with related Centers to stimulate human translation of findings, and implement a dynamic enrichment program. The Behavioral Resource Core B (PI: R.E. Miller; co-director: D.R. Sumner) will provide a centralized resource to facilitate behavioral assays in a broad array of animal models of rheumatic and MSK diseases, including training for behavioral tests, access to customized protocols, equipment, and space to perform testing, a consultation service and a customized, full-service option for behavioral testing. The Neurobiology Core C (PI: RJ Miller; co- director: D.R. Sumner) will offer state-of-the-art techniques for assessment and manipulation of neuronal circuitry involved in pain physiology, such as in vivo calcium imaging, electrophysiology, chemo/optogenetics, transcriptomics/bioinformatics and neuroanatomical techniques. This will allow the Center’s research community to engage in cutting-edge investigations of the mechanisms of pain in animal models of MSK disease. In summary, C-COMP will provide (1) unique resources and infrastructure for supporting high-quality externally funded research and (2) pilot funding, education, and training in a multidisciplinary and collaborative fashion. This integrated approach is expected to accelerate research in pain associated with MSK and rheumatic disease.