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 (TNFa)-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 TNFa 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.