Neurobiology Core C

项目总结 芝加哥肌肉骨骼疼痛中心(C-COMP)的首要目标是促进和支持 研究和培训旨在了解与以下相关的疼痛的潜在机制 肌肉骨骼(MSK)疾病，最终目标是更好地管理和预防它。以支持高- 高质量的创新研究将加速我们对MSK疼痛机制的理解 因此，我们将利用现有的专业知识和 创建神经生物学核心C的资源，该核心C将提供最先进的生理、转录和 神经解剖学工具以及研究MSK疼痛机制的科学专业知识。这些方法 已选择与核心B中提供的行为评估进行协同。 研究外周和中枢神经系统 协调产生疼痛信号在过去十年中变得更加复杂，导致 对慢性疼痛状态背后的神经机制有许多新的见解。我们在拉什和拉什的实验室 西北大学--很大程度上是通过NIAMS资助的资金--在发展方面走在了前列 这些工具特别用于研究MSK疼痛。这些复杂技术的采用 然而，更广泛的MSK领域由于缺乏对大多数实验室的可用性而受到阻碍。这些资源和 为这一核心选择的服务就是为了满足这一需求。我们自己的综合累积经验 (&gt；50年)，并在神经科学和MSK之间建立了创新和国际领先地位 领域，我们在这些不同技术方面的专业知识为我们提供了独特的建议资格 研究MSK疼痛的神经生物学的研究人员。目标1.建立集中评估服务 MSK病临床前模型周围神经系统的生理学变化。这个 CORE将为评估提供咨询、科学知识、技术培训和技术服务 通过使用钙成像，包括体内钙成像，来研究感觉神经元生理学， 电生理学和化学/光遗传学。目标2.建立一个集中的转录本资源 对周围神经系统的分析。该中心将为以下人员提供培训和技术服务 收集和制备背根神经节(DRG)神经元，用于RNA-seq(散装和单细胞)。目标3.提供 研究临床前MSK模型神经解剖学可塑性的集中资源。核心将会 为进行周围神经系统的解剖研究提供技术援助和培训- 特别是关节神经支配，包括关节内神经支配，DRG，RNAScope的免疫组织化学 原位杂交，背根神经节细胞的组织培养，以及标记特定类型细胞的遗传工具(记者 鼠标、AAV)和光片成像。目标4.我们将举办研讨会并提供培训和 为提高C-Comp研究人员对如何在实验中 探索MSK和风湿病的疼痛机制。

Project summary The overarching goal of the Chicago Center on Musculoskeletal Pain (C-COMP) is to foster and support research and training aimed at understanding the mechanisms underlying pain associated with musculoskeletal (MSK) diseases, with the ultimate goal of better managing and preventing it. To support high- quality, innovative research that will accelerate our understanding of the mechanisms underlying MSK pain and, hence, facilitate identification of new therapeutic targets, we will capitalize on existing expertise and resources to create a Neurobiology Core C that will provide state-of-the-art physiological, transcriptomal, and neuroanatomical tools as well as scientific expertise for studying the mechanisms of MSK pain. The methods offered in this core have been chosen to synergize with the behavioral assessments offered in Core B. Technologies for studying the mechanisms through which the peripheral and central nervous systems coordinate to produce pain signaling have become much more sophisticated over the last decade, leading to many new insights into the neural mechanisms underlying chronic pain states. Our laboratories at Rush and Northwestern University - in large parts through NIAMS supported funding - have led the way in developing these tools for use in studying MSK pain in particular. The adoption of these sophisticated techniques in the broader MSK field is, however, hindered by a lack of availability to most laboratories. The resources and services selected for this core have been chosen to fill this need. Our own combined cumulative experience (>50 years) and established innovation and international leadership in bridging the neuroscience and MSK fields, and our expertise in these various technologies provides us with unique qualifications for advising researchers studying the neurobiology of MSK pain. Aim 1. Establish a centralized service for assessing physiological changes in the peripheral nervous system of preclinical models of MSK disease. The Core will provide consultation, scientific expertise, technical training, and technical services for the evaluation of sensory neuron physiology through the use of calcium imaging, including in vivo calcium imaging, electrophysiology, and chemo/opto-genetics. Aim 2. Establish a centralized resource for transcriptomal analysis of the peripheral nervous system. The Core will provide training and technical services for collecting and preparing dorsal root ganglia (DRG) neurons for RNA-seq (bulk and single cell). Aim 3. Provide a centralized resource for studying plasticity in neuroanatomy in preclinical MSK models. The core will provide technical assistance and training for performing anatomical studies of the peripheral nervous system - particularly joint innervation, including intra-articular innervation, immunohistochemistry of DRG, RNAscope in situ hybridization, tissue culture of DRG cells, and genetic tools for labeling particular types of cells (reporter mice, AAVs), and lightsheet imaging. Aim 4. We will present seminars and provide training and enrichment programs for enhancing the understanding of C-COMP investigators in how to experimentally explore mechanisms of pain in MSK and rheumatic diseases.