Lumbar spine muscle degeneration inhibits rehabilitation-induced muscle recovery

腰背痛(LBP)是一种复杂的疾病，影响着65%-85%的人口，是主要的 在美国，肌肉骨骼疾病是导致残疾的原因。腰椎间盘突出症是 最常见的损伤和75%接受手术和康复干预的个人 这种情况的结果不是最理想的或糟糕的。这些患者表现出残疾和缺陷 功能能力，包括腰部肌肉的力量和耐力。肌肉专一性 LBP患者的变化包括肌肉体积改变、脂肪渗透和纤维化以及纤维 区域和类型。重要的是，这些变化对持续性疾病患者的康复不敏感。 慢性或反复出现的症状。虽然在LBP存在的情况下预计会出现正常的与废用相关的萎缩， 更严重或更慢性的病理，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/纤维组织改变，损害肌肉功能和恢复。而当 健康肌肉的结构和适应能力是众所周知的，肌肉恢复在 病理的存在还不太清楚。为了解决这一知识差距，这项提议的目的是 比较急性和非急性肌肉的结构、生理和适应性反应 慢性腰椎病变。我们的中心假设是慢性损伤会导致肌肉的状态 对运动不敏感的炎症、萎缩、纤维化和肌肉退化。特定目标 1将使用核磁共振和直接组织测量来比较宏观和微观结构特性 急性和慢性腰椎间盘损伤患者的多叉肌的变化。《特定目标2》将进行比较 急性冠脉综合征患者多分支被动机械和承重蛋白的变化 以明确慢性腰椎间盘损伤肌肉僵硬增加的机制。在定义的 在一轮术前锻炼中，特定目标3将确定哪些患者对锻炼有反应 检测肌肉肥大、纤维化、炎症和成脂基因表达谱。这些 术后将对患者进行为期6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 创新是因为它利用新的直接组织测试和核磁共振方法来测量肌肉结构， 在活人身上的功能和适应性。我们预计康复工作将立即受到影响，因为 这些发现将提供证据和方法，以确定哪些患者将或将不会对 标准的康复计划。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、手术和康复计划。

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.