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

项目摘要 背痛是全球残疾的主要原因，影响超过1亿美国成年人，椎间盘（IVD） 疾病发挥了重要作用。脊柱手术可以解决疼痛的具体原因，但椎间盘源性疼痛，或轴向疼痛， 以椎间盘退变为最常见诊断的背痛，无特异性且缺乏有效治疗 战略布局来自IVD变性（IVDD）的慢性炎症是导致椎间盘源性疼痛的原因， 基质分解、神经致敏和神经血管向内生长;以及纤维环引起炎症 纤维（AF）和终板（EP）缺损，愈合不良，导致IVD高度丢失、椎管狭窄， 生物力学不稳定性椎间盘源性疼痛的有效管理技术需要重新思考我们如何 了解这种情况，这个项目确定了IVD和神经病理学的作用，重点是如何 IVD损伤导致脊髓（SC）致敏和重塑。 多样性补充增加了SC背角的测量， 重点关注IVD和外周神经系统的父母资助。概念、方法和目标是 因此，与增加SC的父母补助金保持一致和平行。 多样性补充是SC重塑和致敏是急性IVD损伤之间的关键因素， 和慢性疼痛反应。具体而言，急性椎间盘损伤通过肿瘤进展为慢性椎间盘源性疼痛， 坏死因子α（TNFα）调节的IVD变性和SC致敏和重塑。我们也 探讨SC重构与IVD退变及背根节重构的关系， 为了更好地了解慢性IVDD的病理生理学相关性，以及早期TNFα调节如何能够 改变这个进程。Kashaf Zaheer女士是一位杰出的学士后候选人， 代表性不足的群体和弱势背景。研究和指导计划旨在 加快扎希尔女士的研究专长，并促进扎希尔女士的录取成为顶级MD/博士 程序.关键要素是提供大量的科学培训，广泛的指导，课程和同行 网络，专业发展和网络。

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.