Lumbar spine muscle degeneration inhibits rehabilitation-induced muscle recovery

腰椎肌肉退化抑制康复引起的肌肉恢复

• 批准号: 9896864
• 负责人: Samuel Richard Ward
• 金额: $ 30.63万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9896864
• 关键词: Activities of Daily Living; Acute; Address; Affect; Age; Area; Atrophic; Biological; CASP1 gene; Cell Count; Chronic; Collagen; Complex; Conflict (Psychology); Exercise; Expression Profiling; Extracellular Matrix; FRAP1 gene; Fascicle; Fatty acid glycerol esters; Fiber; Fibrosis; Gene Expression; Health Care Costs; Hour; Human; Hypertrophy; Imaging Techniques; Impairment; Incidence; Individual; Infiltration; Inflammation; Inflammatory; Injury; Intervention; Knowledge; Low Back Pain; Magnetic Resonance Imaging; Measurement; Measures; Mechanics; Medication Management; Methods; Microscopic; Muscle; Muscle function; Musculoskeletal; Operative Surgical Procedures; Outcome; PPAR gamma; Pain management; Pathologic; Pathology; Pathway interactions; Patients; Pharmacology; Physiological; Population; Postoperative Period; Predisposition; Property; Proteins; Recovery; Recovery of Function; Recurrence; Recurrent Low Back Pain; Rehabilitation therapy; Reporting; Resistance; Skeletal Muscle; Source; Spinal Injuries; Structure; Symptoms; TNF gene; Testing; Tissues; Transforming Growth Factor beta; United States; Vertebral column; Weight-Bearing state; base; cost; disability; experience; experimental study; functional loss; functional restoration; in vivo; innovation; mechanical load; mechanical properties; muscle degeneration; muscle hypertrophy; muscle stiffness; muscular structure; novel; pain relief; persistent symptom; precision medicine; programs; response; satellite cell; success; treatment response; vastus lateralis

Low back pain (LBP) is a complex condition that affects 65-85% of the population, and is the leading musculoskeletal condition contributing to disability in the United States. Disc herniation injuries are the most common injury and 75% of individuals undergoing surgical and rehabilitative interventions for this condition experience suboptimal or poor outcomes. These patients demonstrate disability and deficits in functional capacity, including strength and endurance of the lumbar musculature. Muscle-specific changes in individuals with LBP include altered muscle volume, fatty infiltration and fibrosis, and fiber area and type. Importantly, these changes are insensitive to rehabilitation in patients with continued chronic or recurrent symptoms. While normal disuse-related atrophy in the presence of LBP is expected, more severe or chronic pathology, such as inflammation and fiber damage, may be inducing irreversible fiber degeneration and fatty/fibrotic tissue changes that impair muscle function and recovery. While the structural and adaptive capacities of healthy muscle are well understood, muscle recovery in the presence of pathology is less clear. To address this gap in knowledge, the purpose of this proposal is to compare structural, physiological, and adaptive responses of muscle in the presence of acute and chronic lumbar spine pathology. Our central hypothesis is that chronic injury results in a state of muscle inflammation, atrophy, fibrosis, and muscle degeneration that is not responsive to exercise. Specific Aim 1 will use MRI and direct tissue measurements to compare macro and microscopic structural properties of multifidus muscles in patients with acute versus chronic lumbar disc injury. Specific Aim 2 will compare the passive mechanical and load-bearing protein changes in the multifidus of patients with acute versus chronic lumbar disc injury to identify the mechanism of increased muscle stiffness. Following a defined bout of pre-operative exercise, Specific Aim 3 will identify which patients respond to exercise by examining muscle hypertrophic, fibrotic, inflammatory, and adipogenic gene expression profiles. These patients will be followed for six months post-operatively to measure muscle recovery and strength. These experiments will elucidate the structural, mechanical, and adaptive potential of lumbar spine muscles in these patients. This contribution is significant because it is the first step in a precision medicine approach aimed at reversing atrophic or degenerative muscle changes that obstruct patient recovery. The proposal is innovative because it utilizes novel direct tissue testing and MRI methods to measure muscle structure, function, and adaptation in living humans. We expect an immediate impact on rehabilitation because these findings will provide evidence and methods for identifying patients who will or will not respond to standard rehabilitation programs. In the long-term, we expect these experiments will provide direction for unique, patient-specific pharmacological, surgical and rehabilitation programs.

腰痛 (LBP) 是一种复杂的疾病，影响着 65-85% 的人口，并且是主要的疾病 在美国，肌肉骨骼疾病导致残疾。椎间盘突出损伤是 最常见的伤害，75% 的人为此接受手术和康复干预 状况经历次优或不良结果。这些患者表现出残疾和缺陷 功能能力，包括腰部肌肉组织的力量和耐力。肌肉特异性 LBP 患者的变化包括肌肉体积改变、脂肪浸润和纤维化以及纤维 面积和类型。重要的是，这些变化对持续治疗的患者的康复不敏感。 慢性或反复出现的症状。虽然 LBP 存在时预计会出现正常的废用相关萎缩， 更严重或慢性的病理，例如炎症和纤维损伤，可能会导致不可逆转的 纤维变性和脂肪/纤维化组织变化会损害肌肉功能和恢复。虽然 健康肌肉的结构和适应能力已被充分了解，肌肉恢复 病理的存在不太清楚。为了解决这一知识差距，本提案的目的是 比较肌肉在急性和急性发作时的结构、生理和适应性反应 慢性腰椎病理学。我们的中心假设是慢性损伤会导致肌肉处于一种状态 炎症、萎缩、纤维化和对运动无反应的肌肉变性。具体目标 1 将使用 MRI 和直接组织测量来比较宏观和微观结构特性 急性与慢性腰椎间盘损伤患者的多裂肌的变化。具体目标2将进行比较 急性和慢性疾病患者多裂肌的被动机械和承重蛋白变化 慢性腰椎间盘损伤以确定肌肉僵硬增加的机制。遵循定义的 一轮术前锻炼，具体目标 3 将通过以下方式确定哪些患者对锻炼有反应 检查肌肉肥大、纤维化、炎症和脂肪形成基因表达谱。这些 术后将对患者进行六个月的随访，以测量肌肉恢复和力量。这些 实验将阐明腰椎肌肉的结构、机械和适应性潜力 这些病人。这一贡献意义重大，因为它是精准医学方法的第一步 旨在逆转阻碍患者康复的萎缩或退行性肌肉变化。该提案是 创新，因为它利用新颖的直接组织测试和 MRI 方法来测量肌肉结构， 活人类的功能和适应。我们预计会对康复产生立竿见影的影响，因为 这些发现将为识别哪些患者会做出反应或不会做出反应提供证据和方法 标准康复计划。从长远来看，我们预计这些实验将为 独特的、针对患者的药理学、手术和康复计划。