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，