Human Nociceptor and Spinal Cord Molecular Signature Center

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Our collaborative groups, led by Drs. Price at UT Dallas (UTD), Dougherty at MD Anderson Cancer Center (MDACC) and Curatolo at University of Washington (UW), have been on the forefront of using human dorsal root ganglion (DRG) and other tissues to understand mechanisms that cause chronic pain in patients. Our work is on the leading edge of transcriptomic studies that have revealed unique features of the human DRG at the single neuron level. The goal of this project is to create the scientific foundation that will empower pain researchers around the world to approach the problem of treating pain in a new way, deeply rooted in a fundamental understanding of the first neurons and first synapses in the pain pathway. Our Center will focus on two prioritized aims. The first is identifying molecular phenotypes, using single cell and spatial transcriptomic technologies, of human sensory neurons from the DRG in organ donor recovered tissues and in patients suffering from chronic pain who are having surgeries where DRGs or peripheral nerves are removed. We will use this information to understand how nociceptors are activated in chronic pain disorders, with a focus on neuropathic pain, chronic neck pain and low back pain. These chronic pain disorders are the most disabling and the latter two are poorly modeled in animals. The second is to use spinal cord recovered from organ donors for single cell and spatial profiling with the goal of understanding the connectome of the human pain pathway at the first synapse. We will provide an integrated view of how nociceptors likely communicate with spinal cord neurons with the goal of understanding the pharmacology of projection neurons that send nociceptive signals to the brain to create pain perception. Our established collaboration and demonstrated track record of productivity ensures the success of this complex project. We envision creating actionable knowledge and data resources that can transform our understanding of human pain conditions leading to the generation of the treatments pain patients need.