The Role of Disc Nutrition in the Etiology and Clinical Treatment of Disc Degeneration

椎间盘营养在椎间盘退变的病因学和临床治疗中的作用

• 批准号: 10531879
• 负责人: SARAH E GULLBRAND
• 金额: --
• 依托单位: PHILADELPHIA VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10531879
• 关键词: Adult; Affect; Animal Model; Animals; Area; Articular Range of Motion; Atomic Force Microscopy; Back Pain; Biochemistry; Biological Assay; Biology; Blood Vessels; Bone Density; Cadaver; Caregivers; Caring; Cartilage; Cells; Clinical; Clinical Research; Clinical Treatment; Convection; Custom; Devices; Diffusion; Economic Burden; Etiology; Euthanasia; Faculty; Fibrocartilages; Funding; Gene Expression Profiling; General Population; Goals; Health; Heart; Histology; Homeostasis; Human; Image; Incidence; Intervertebral disc structure; K-Series Research Career Programs; Knowledge; Link; Location; Low Back Pain; Magnetic Resonance Imaging; Malignant Neoplasms; Maps; Measurement; Measures; Mechanics; Mentors; Microfils; Military Personnel; Modeling; Motion; Needles; Nutrient; Nutritional; Oryctolagus cuniculus; Outcome; Pain; Pathway interactions; Patient-Focused Outcomes; Patients; Physical therapy; Play; Positioning Attribute; Prevalence; Property; Puncture procedure; Questionnaires; Regimen; Research; Research Activity; Research Personnel; Role; Sampling; Severities; Source; Spectroscopy, Fourier Transform Infrared; Spinal; Stroke; Structure; Time; Tissue Engineering; Training; Transport Process; Travel; United States; Vertebral column; Veterans; Visual; Waste Products; Weight-Bearing state; Work; active duty; analog; bone; career development; chronic pain; contrast enhanced; density; disability; disc regeneration; distraction; efficacious treatment; experience; fluid flow; functional outcomes; improved; in vivo; indexing; intervertebral disk degeneration; mechanical load; mechanical properties; mineralization; nucleus pulposus; nutrition; pain relief; patient response; predictive tools; regenerative; response; skills; small molecule; social; spine bone structure; success; treatment strategy; vertebra body; wasting

Low back pain, most commonly caused by degeneration of the intervertebral disc, places a significant social and economic burden on the general public, active duty military and veterans alike. The intervertebral discs of the spine are the largest avascular structures in the body, and the cells within the disc therefore rely on the transport of nutrients and waste products across the vertebral endplate to maintain disc homeostasis. A compromise in transport across the vertebral endplate interface is therefore implicated in the initiation and progression of disc degeneration. The overarching goal of this proposal is twofold: (1) Elucidate the properties of the boney and cartilage endplates that affect trans-endplate transport and how alterations in transport contribute to disc degeneration, and (2) investigate alterations to trans-endplate transport and disc health during non-operative treatment of patients with back pain and their correlation with pain relief and functional outcomes. These goals will be accomplished via the following specific aims: Aim 1: Determine the structural, mechanical and compositional properties of the vertebral endplates affecting diffusion and convection into healthy and degenerative human intervertebral discs. A custom MRI-compatible device will be constructed to quantify the transport properties of cadaveric human endplate samples under both diffusion and convection (fluid flow). Transport properties will then be correlated with boney endplate compositional and local mechanical properties, as assayed via µCT, histology, Fourier transform infrared spectroscopy (FTIR), local strain tracking analysis, and atomic force microscopy (AFM). Aim 2: Establish correlations between intervertebral disc degeneration, trans-endplate small molecule diffusion, and vertebral endplate structure, composition and mechanics in an in vivo rabbit model. Intervertebral disc degeneration will be induced in vivo in a rabbit model via puncture of the disc with a 16G or 21G needle. Animals will be euthanized at 4, 8, and 16 weeks post-puncture to generate a spectrum of degeneration from mild (21G puncture) to severe (16G puncture). Small molecule trans-endplate diffusion into the disc will be quantified via post-contrast enhanced MRI T1-mapping. The boney and cartilage endplates will be assayed via microFil enhanced µCT to determine bone and vascular density. Composition and mechanics of the endplates will be assayed via FTIR and AFM, respectively. Degeneration of the intervertebral disc will be assessed via MRI T2-mapping, histology, biochemistry and gene expression assays. Aim 3: Determine the feasibility and preliminary outcomes of quantifying the effect of physical therapy on trans-endplate diffusion into the degenerative disc in patients with back pain. Human patients with back pain concomitant with disc degeneration will be subjected to MRI T2- mapping and post-contrast enhanced T1-mapping at time points prior to and 6 weeks after physical therapy. Standard questionnaires of pain (visual analog scale), function (Oswestry Disability Index), as well as objective measures of lumbar range of motion, will be completed at the same time points to establish correlations between disc health, nutrition and patient outcomes.

腰痛，最常见的原因是椎间盘退变， 给广大公众、现役军人带来沉重的社会和经济负担 军人和退伍军人都一样。脊柱的椎间盘是最大的无血管 因此，体内的结构和椎间盘内的细胞依赖于运输 营养物质和废物穿过椎体终板以维持椎间盘 体内平衡。穿过椎体终板界面的运输的妥协是 因此涉及椎间盘退变的起始和进展。这 该提案的总体目标有两个：（1）阐明骨性和骨性的特性。 影响跨终板运输的软骨终板以及运输的改变 导致椎间盘退变，以及（2）研究跨终板的改变 背痛患者非手术治疗期间的运输和椎间盘健康 它们与疼痛缓解和功能结果的相关性。这些目标将是 通过以下具体目标来实现： 目标 1：确定结构、 影响扩散的椎体终板的机械和成分特性 以及对流进入健康和退化的人类椎间盘。定制 将构建与 MRI 兼容的设备来量化 扩散和对流（流体流动）下的人体终板样本。 然后，运输特性将与骨终板成分和局部相关 机械性能，通过 µCT、组织学、傅里叶变换红外测定 光谱（FTIR）、局部应变跟踪分析和原子力显微镜（AFM）。 目标 2：建立椎间盘退变、跨终板之间的相关性 小分子扩散和椎体终板结构、成分和力学 体内兔子模型。将在兔子体内诱导椎间盘退变 通过使用 16G 或 21G 针穿刺椎间盘来建立模型。动物将被安乐死 穿刺后 4、8 和 16 周产生从轻度到退化的一系列变化 （21G穿刺）至重度（16G穿刺）。小分子跨终板扩散到 椎间盘将通过对比后增强 MRI T1 映射进行量化。骨头和 软骨终板将通过 microFil 增强 µCT 进行分析，以确定骨和 血管密度。将通过 FTIR 分析终板的成分和力学 和 AFM 分别。将通过 MRI 评估椎间盘退变情况 T2 绘图、组织学、生物化学和基因表达测定。目标 3：确定 量化物理治疗效果的可行性和初步结果 背痛患者经终板扩散至退变椎间盘。人类 伴有椎间盘退变的背痛患者将接受 MRI T2- 之前和 6 周时间点的标测和对比后增强 T1 标测 物理治疗后。疼痛（视觉模拟量表）、功能的标准问卷 （Oswestry 残疾指数）以及腰椎运动范围的客观测量， 将在同一时间点完成，以建立椎间盘健康状况之间的相关性， 营养和患者结果。