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: 10311070
• 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/10311070
• 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; Diffuse; Diffusion; Economic Burden; Etiology; 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; Measurement; Measures; Mechanics; Mentors; Microfils; 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; base; 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; military veteran; 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.

腰部疼痛，最常见的原因是椎间盘退变， 将重大的社会和经济负担强加给普通公众、现役军人 军人和退伍军人都一样。脊柱的间盘是最大的无血管的 体内的结构，以及盘内的细胞因此依赖于 营养物质和废物横跨椎体终板以维持椎间盘 动态平衡。在通过椎体终板界面的运输中的折衷是 因此与椎间盘退变的发生和发展有关。这个 这一建议的首要目标有两个：(1)阐明骨和骨的性质 影响跨终板运输的软骨终板及其在运输中的变化 导致椎间盘退变，以及(2)调查横过终板的改变 腰背痛患者非手术治疗过程中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 通过以下具体目标实现：目标1：确定结构， 影响扩散的椎体终板的力学和成分特性 并对流到健康和退化的人类间盘中。一种习俗 将构建与MRI兼容的设备来量化药物的传输特性 人体身体终板样品在扩散和对流(流体流动)下。 然后将传输特性与骨终板的成分和局部相关联 力学性能通过µCT、组织学、傅里叶变换红外进行分析 光谱(FTIR)、局部应变跟踪分析和原子力显微镜(AFM)。 目的2：建立椎间盘退变、经终板 小分子扩散与椎体终板结构、成分和力学 活体兔模型。兔在体椎间盘退变的实验研究 用16G或21G针穿刺椎间盘模型。动物将在2019年被实施安乐死 穿刺术后4周、8周和16周产生轻度退行性变的谱系 (21g穿刺法)至重度(16g穿刺法)。小分子跨端板扩散进入 该间盘将通过增强后MRI T1图进行量化。骨瘦如柴 软骨终板将通过MicroFil增强µCT进行分析，以确定骨骼和 血管密度。端板的成分和机械性能将通过FTIR进行分析 和原子力显微镜。椎间盘退变将通过核磁共振进行评估 T2定位、组织学、生化和基因表达分析。目标3：确定 物理疗法疗效量化的可行性和初步结果 背部疼痛患者经终板扩散进入退变的椎间盘。人类 伴有腰椎退变的背痛患者将接受磁共振T2扫描。 标测和增强后T1标测在6周前和6周的时间点 在理疗之后。疼痛(视觉模拟评分)、功能的标准问卷 以及腰椎活动范围的客观测量， 将在相同的时间点完成以建立盘健康之间的关联， 营养和患者结局。