Anti-inflammatory Cell Based Repair of Intervertebral Disc Degeneration

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Project Abstract Discogenic back pain, is a leading cause of disability, and involves degenerative changes of the intervertebral disc (IVD), including matrix degradation, altered cell shape and phenotype, inflammation, and pathological nerve ingrowth. Since only a small subset of patients responds favorably to conventional treatments which address the symptoms but not the disease, there is a need for new therapies to treat disc degeneration (DD). Pro-inflammatory cytokines, which are associated with painful DD, lower the threshold for pain and lead to an exaggerated pain response or increased pain sensitivity (hyperalgesia). In the parent award, we are identifying strategies to reduce the pro-inflammatory and enhance the anti-inflammatory responses of bone marrow derived MSCs treatment for IVD repair. Therefore, the goal of this project is to examine ‘bidirectional interaction between injured painful IVD and sensory nerves’, an area of interest described in NOT-AR-23-015. The goal of this project is to define the innervation and phenotype of the sensory neurons innervating the caudal IVD, and to assess changes in the DRGs of the innervating neurons with injury and mesenchymal stem cell (MSC) treatment. This project meets Goal A, to generate supporting evidence towards a future innovative study and new scientific direction in pain research in musculoskeletal diseases. Aim S1 studies will spatially map the sensory neural innervation of the rat caudal IVD. Aim S2 studies will identify changes in the molecular signatures of DRG populations and DRG sensitization with caudal IVD injury and anti- inflammatory cell treatment. This project will stimulate substantial innovations on pain research approaches and methodologies. Completion of this work will provide markers for new, functionally distinct sensory neurons relevant to painful IVDs. The resulting catalog will also illustrate the diversity of sensory types and the cellular complexity underlying painful sensation due to musculoskeletal degeneration, injury and treatment.