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

多样性补充：TNFα 在椎间盘源性疼痛进展中的作用以及作为治疗目标

• 批准号: 10631481
• 负责人: James C. Iatridis
• 金额: $ 3.26万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10631481
• 关键词: Acute; Address; Admission activity; Adult; Back Pain; Biomechanics; Chronic; Defect; Development; Diagnosis; Disease; Doctor of Philosophy; Elements; Functional disorder; Height; Inflammation; Institution; Intervertebral disc structure; Measurement; Mentors; Methods; Pain; Peripheral Nervous System; Play; Research; Role; Spinal Cord; Spinal Stenosis; Spinal cord posterior horn; Spine surgery; TNF gene; Techniques; Thinking; Training; Training Programs; Underrepresented Populations; chronic pain; design; disability impact; disadvantaged background; discogenic pain; effective therapy; healing; intervertebral disk degeneration; neuropathology; neurovascular; parent grant; peer networks; programs; recruit; relating to nervous system; response; spinal disk injury; spinal nerve posterior root; treatment strategy

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.

项目概要 背痛是全球残疾的主要原因，影响超过 1 亿患有椎间盘突出 (IVD) 的美国成年人 脊柱手术可以解决疼痛的特定原因，但椎间盘源性疼痛或轴性疼痛。 以 IVD 变性为最常见诊断的背痛是非特异性的并且缺乏有效的治疗 IVD 变性 (IVDD) 引起的慢性炎症是导致椎间盘源性疼痛的原因之一。 基质破坏、神经敏化、神经血管向内生长和纤维环引起炎症； 纤维组织 (AF) 和终板 (EP) 缺陷愈合不良并导致 IVD 身高下降、椎管狭窄和 椎间盘源性疼痛的生物力学不稳定性的有效管理技术需要重新思考我们如何 了解这种情况，该项目确定了 IVD 和神经病理学的作用，重点是如何 IVD 损伤导致脊髓 (SC) 敏化和重塑。 多样性增刊将 SC 背角的测量添加到了 专注于 IVD 和周围神经系统的家长资助。 因此，与添加 SC 的家长补助金保持一致并平行 这是其科学前提。 多样性补充是 SC 重塑和致敏是急性 IVD 损伤的关键区别 具体来说，急性 IVD 损伤通过肿瘤发展为慢性椎间盘源性疼痛。 我们还研究了坏死因子 α (TNFα) 调节的 IVD 变性和 SC 致敏和重塑。 研究 SC 重塑与 IVD 变性和背根神经节重塑之间的关系， 更好地了解与慢性 IVDD 的病理生理学关联，以及早期 TNFα 调节如何 Kashaf Zaheer 女士是一名出色的学士后候选人。 研究和指导计划旨在针对代表性不足的群体和弱势群体。 加速 Zaheer 女士的研究专业知识，并促进 Zaheer 女士进入顶级医学博士/博士学位 计划的关键要素是提供大量的科学培训、广泛的指导、课程作业和同伴。 网络、专业发展和网络。