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.

项目摘要 背痛是全球残疾影响> 1亿美国成年人的主要原因，椎间盘（IVD） 疾病起着主要作用。脊柱手术可以解决疼痛的特定原因，但腹部疼痛或轴向 以IVD变性为最常见的诊断性的背痛是非特异性诊断的，并且缺乏有效的治疗 策略。 IVD变性（IVDD）的慢性炎症是导致椎间内疼痛的原因，导致 基质分解，神经敏化和神经血管内部；和炎症是由环引起的 纤维纤维（AF）和终板（EP）缺陷，愈合不佳，导致IVD身高损失，脊柱狭窄和 生物力学不稳定性。有效的椎间盘痛的管理技术需要重新思考我们的方式 了解这种情况，该项目确定了IVD和神经病理学的角色，重点是 IVD损伤导致脊髓（SC）灵敏度和重塑。 多样性补充剂增加了SC背角的测量结果 父母赠款专注于IVD和外周神经系统。概念，方法和目标是 因此，与添加sc保持一致并与父母的授予相一致。科学前提 多样性补充是SC重塑和灵敏度是急性IVD损伤之间的关键区别者 和慢性疼痛反应。具体而言，急性IVD损伤通过肿瘤发展为慢性椎间盘突出疼痛 坏死因子α（TNFα）调节的IVD变性和SC敏感性和重塑。我们也是 研究与IVD变性和背根神经化重塑之间的SC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TNFα调制如何可以 改变这种进展。 Kashaf Zaheer女士是一位出色的后库后候选人 代表性不足的群体和处境不利的背景。研究和心理计划旨在 加速Zaheer女士的研究专业知识，并将Zaheer女士的录取晋升为顶级医学博士学位 程序。关键要素是提供大量的科学培训，广泛的心理，课程和同伴 网络，专业发展与网络。