Mechanistic structure-function relationships for paraspinal muscle fat infiltration in chronic low back pain patients

项目摘要 慢性下背痛（cLBP）是世界上最主要的衰弱性疾病，也是最常见的原因。 阿片类药物在美国虽然轴向cLBP通常被认为是非特异性和多因素的，但它是 通常怀疑包括椎间盘（IVD）在内的脊柱稳定系统功能障碍， 邻近的椎旁肌（PSM）。由于不确定性，轴向cLBP的治疗具有众所周知的挑战性 关于患者特异性因果机制阻止有效匹配治疗。IVD变性是 很容易通过临床影像学检查并经常进行研究。对PSM变性的作用知之甚少， 包括萎缩和脂肪浸润（FI），这被认为与cLBP有关，尽管现有的证据 没有明确的关联。鉴于可量化FI的先进MRI序列的可用性， 可能调查PSM FI模式，这将告知它如何与cLBP的功能结局相关 患者 目前的工作假设是，退行性IVD病理学促进PSM FI是由于 肌肉的代偿性生物力学反应，试图稳定受影响的脊柱节段， 超时导致神经肌肉疲劳和/或直接暴露于IVD的促炎因子 损害我们假设PSM FI空间分布模式（脂肪图）与1） 患者特异性运动学和PSM激活模式（即运动控制），和2）双分子因素，推导 从PSM病人的肌肉活检中为了检验这一假设，我们将量化PSM FI，退行性IVD病理， 躯干和全身运动学，以及椎旁肌肉激活，40例轴向cLBP受试者和40例年龄匹配的 对照我们还将收集cLBP患者的肌肉组织样本，以揭示生物分子 PSM FI的机制。在这项研究中，我们建议1）量化椎旁肌的空间分布 脂肪浸润并将产生的脂肪图与cLBP和退行性IVD病理学相关联，2）量化运动 来自多域肌肉激活和运动学数据类型的控制模式，并与cLBP相关联 症状和PSM FI，以及3）揭示不同PSM FI的潜在生物分子机制 和运动控制模式。这项研究是为了调查不同的原因而设计的 研究PSM如何在轴性cLBP患者中被脂肪浸润，此外， cLBP患者中与PSM FI相关的功能结局。这项工作将促进我们对 PSM FI与cLBP相关的临床相关性和因果机制，并为未来使用PSM提供信息 FI作为成像生物标志物，用于优化特定肌肉靶向cLBP治疗的患者选择， 改善成果。

PROJECT SUMMARY Chronic low back pain (cLBP) is the world's leading debilitating condition and the most common reason for opioid prescription in the US. While axial cLBP is commonly considered non-specific and multifactorial, it is often suspected a dysfunction of the spinal stabilization system that includes the intervertebral disc (IVD) and adjacent paraspinal muscles (PSMs). Axial cLBP is notoriously challenging to treat because of uncertainty about patient-specific causal mechanisms preventing effective matching to treatments. IVD degeneration is easily appreciated with clinical imaging and often studied. Less is known about the role of PSM degeneration, including atrophy and fat infiltration (FI), which are assumed to relate to cLBP, although existing evidence does not provide a clear association. Given the availability of advanced MRI sequences that quantify FI, it is now possible to investigate PSM FI patterns that will inform how it may relate to functional outcomes in cLBP patients. The current working hypothesis is that degenerative IVD pathology promotes PSM FI as a result of a compensatory biomechanical response of the muscle in an attempt to stabilize an affected spinal segment that overtime leads to neuromuscular fatigue and/or from direct exposure to pro-inflammatory factors from IVD damage. We hypothesize that PSM FI spatial distribution patterns (fat maps) have significant correlation with 1) patient-specific kinematics and PSM activation patterns (i.e. motor control), and 2) bimolecular factors, derived from patient PSM muscle biopsy. To test this hypothesis, we will quantify PSM FI, degenerative IVD pathology, trunk and full-body kinematics, and paraspinal muscle activation in 40 axial cLBP subjects and 40 age-matched controls. We will also collect a muscle tissue sample from the cLBP patients to uncover the biomolecular mechanisms of PSM FI. In this study, we are proposing to 1) quantify spatial distribution of paraspinal muscle fat infiltration and associate resulting fat maps with cLBP and degenerative IVD pathology, 2) quantify motor control patterns from multi-domain muscle activation and kinematics data types and associate with cLBP symptoms and PSM FI, and 3) uncover different potential biomolecular mechanisms underlying distinct PSM FI and motor control patterns in cLBP patients. This study has been uniquely crafted to investigate different reasons for how PSM might become infiltrated with fat in axial cLBP patients and, furthermore, the potentially disabling functional outcomes associated with PSM FI in cLBP patients. This work will advance our understanding of the clinical relevance and causal mechanisms of PSM FI in relation to cLBP and inform future efforts to use PSM FI as an imaging biomarker to optimize patient-selection for specific muscle-targeting cLBP therapies to improve outcomes.