Diversity Supplement for: Role of TNFalpha in discogenic pain progression and as a treatment target

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PROJECT SUMMARY Back pain is a leading cause of global disability impacting >100 million US adults, with intervertebral disc (IVD) disorders playing a major role. Spinal surgery can address specific causes of pain, yet discogenic pain, or axial back pain with IVD degeneration as the most common diagnosis, is non-specific and lacks effective treatment strategies. Chronic inflammation from IVD degeneration (IVDD) is a cause of discogenic pain resulting in matrix breakdown, neural sensitization, and neurovascular ingrowth; and inflammation arises from annulus fibrosus (AF) and endplate (EP) defects that heal poorly and result in IVD height loss, spinal stenosis, and biomechanical instability. Effective management techniques for discogenic pain requires re-thinking how we understand this condition, and this project identifies roles of both IVDs and neuropathology with a focus on how IVD injury results in spinal cord (SC) sensitization and remodeling. The Diversity Supplement adds measurements of the dorsal horn of the SC to the studies proposed in the parent grant that focused on IVD and peripheral nervous system. The concept, methods, and Aims are therefore aligned with and parallel the parent grant with the addition of SC. The scientific premise of this Diversity Supplement is that SC remodeling and sensitization are a key distinguisher between acute IVD injury and chronic pain responses. Specifically, that acute IVD injuries progress to chronic discogenic pain via tumor necrosis factor alpha (TNFα)-modulated IVD degeneration and SC sensitization and remodeling. We also investigate the relationship between SC remodeling with IVD degeneration and dorsal root ganglio remodeling, to better understand the pathophysiology association with chronic IVDD, and how early TNFα modulation can change that progression. Ms. Kashaf Zaheer is an outstanding postbaccalaureate candidate from an underrepresented group and disadvantaged background. The research and mentoring plans are designed to accelerate Ms. Zaheer's research expertise and promote Ms. Zaheer's admissions into a top MD/PhD program. Key elements are to provide substantial scientific training, extensive mentoring, coursework & peer networking, and professional development & networking.