Neurobiology Core C

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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.