Phenotypes of pathologic vertebral endplate degeneration

病理性椎体终板退变的表型

• 批准号: 8584145
• 负责人: JEFFREY C. LOTZ
• 金额: $ 60.22万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8584145
• 关键词: Address; Adult; Affect; Anatomy; Architecture; Area; Attention; Back Pain; Biological Markers; Biomechanics; Bone Marrow; Cadaver; Caring; Cartilage; Chronic low back pain; Clinical; Computer Simulation; Data; Defect; Development; Diagnosis; Diagnostic; Elements; Functional disorder; Future; Goals; Granulation Tissue; Harvest; Hematopoietic; Histologic; Human; Image; Imaging Device; Imaging technology; Individual; Inflammation; Intervertebral disc structure; Lesion; Link; Logistic Regressions; Low Back Pain; Magnetic Resonance Imaging; Measures; Modality; Modeling; Morbidity - disease rate; Musculoskeletal; Pain; Pain Research; Pain management; Painless; Pathologic; Pathologic Processes; Pathology; Patient Care; Patients; Peripheral; Phenotype; Population; Porosity; Prevention strategy; Procedures; Process; Property; Receiver Operator Characteristics; Recruitment Activity; Research; Resolution; Risk; Risk Factors; Sampling; Scheme; Secondary to; Sensitivity and Specificity; Source; Spinal; Structure; Symptoms; Techniques; Testing; Therapeutic Intervention; Thick; Time; Tissues; Uncertainty; Vertebral column; Weight; Work; base; bone; improved; intervertebral disk degeneration; nerve supply; prognostic; public health relevance; spine bone structure; tool; volunteer

DESCRIPTION (provided by applicant): Low back pain is a significant cause of morbidity and societal expense, affecting between 65% and 80% of the population at least once in their lifetime. The intervertebral disc is thought to be a primary pain source, but mechanisms by which discs degenerate and hurt are poorly understood. There has been little attention paid to cross talk between discs and adjacent vertebra in relation to degeneration and pain. Historical data suggest that the vertebral endplate can be a significant source of pain in some 'discogenic' patients, but little is known about the pathophysiology of this process. We propose to study the endplates and discs in human cadaver spines to clarify pathologic processes and validate new imaging technologies that may serve as sensitive biomarkers for localizing painful spinal levels and directing patients toward ideal therapies. These new imaging grading schemes will be tested in patients with confirmed discogenic low back pain and control asymmetric volunteers. Three aims are proposed. In Aim 1 we will validate quantitative techniques for MR-based depictions of endplate and annular damage using fresh human cadaveric lumbar spines, and establish whether pathologic endplate phenotypes associate with intrinsic vertebral abnormalities, or rather are secondary to adjacent disc pathology. In Aim 2 we reveal structural risk factors for endplate damage and disc degeneration using high- resolution computational models. In Aim 3 we will test whether techniques developed in Aim 1 are sensitive and specific for discogenic low back pain. Through this work, we plan to clarify pathologic processes within vertebral endplates and develop more sensitive clinical imaging tools. Future studies will focus on clarifying mechanisms for the innervated disc pathologies that are linked to symptoms in patients.

描述(申请人提供)：腰痛是发病率和社会费用的重要原因，65%到80%的人一生中至少有一次受到影响。椎间盘被认为是主要的疼痛来源，但对椎间盘退变和损伤的机制知之甚少。很少有人注意到椎间盘和相邻椎体之间的串扰与退变和疼痛的关系。历史数据表明，椎体终板可能是一些“间盘”患者疼痛的重要来源，但对这一过程的病理生理学知之甚少。我们建议研究人类身体脊柱的终板和椎间盘，以阐明病理过程，并验证新的成像技术，这些技术可以作为定位疼痛脊柱平面和指导患者走向理想治疗的敏感生物标志物。这些新的成像分级方案将在确诊为椎间盘源性下腰痛的患者和对照不对称志愿者中进行测试。提出了三个目标。在目标1中，我们将使用新鲜的人身体腰椎验证基于MR的终板和环状损伤的定量技术，并确定病理终板的表型是否与固有的椎体异常相关，或者更确切地说，是继发于邻近的椎间盘病理。在目标2中，我们使用高分辨率计算模型揭示了终板损伤和椎间盘退变的结构性风险因素。在目标3中，我们将测试在目标1中开发的技术是否对椎间盘源性下腰痛敏感和特异。通过这项工作，我们计划阐明椎体终板内的病理过程，并开发更灵敏的临床成像工具。未来的研究将集中在阐明与患者症状有关的神经性椎间盘病理的机制。