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

项目总结 慢性下腰痛(CLBP)是世界上最主要的衰弱疾病，也是导致 美国的阿片类药物处方。虽然轴性cLBP通常被认为是非特异性和多因素的，但它是 常被怀疑为脊柱稳定系统功能障碍，包括间盘(IVD)和 毗邻的椎旁肌(PSM)。由于不确定性，轴型cLBP的治疗难度是出了名的。 关于阻止有效匹配治疗的患者特定的因果机制。IVD变性是 临床影像容易欣赏，经常研究。对PSM退行性变的作用知之甚少， 包括萎缩和脂肪渗透(FI)，这被认为与cLBP有关，尽管现有证据确实如此 没有提供明确的关联。鉴于可以量化FI的先进磁共振成像序列的可用性，现在是 可能研究PSM FI模式，以告知它可能如何与cLBP的功能结局相关 病人。 目前的工作假设是退行性IVD病理促进了PSM FI，这是一种 肌肉的代偿性生物力学反应，试图稳定受影响的脊柱节段， 超时工作会导致神经肌肉疲劳和/或直接暴露于IVD的促炎因子 损坏。我们假设PSM FI空间分布模式(FAT图)与1)有显著的相关性 患者特定的运动学和PSM激活模式(即运动控制)，以及2)双分子因素，得出 取自患者的PSM肌肉活组织检查。为了验证这一假设，我们将量化PSM FI，退行性IVD病理， 40例枢椎cLBP受试者和40例年龄匹配患者的躯干和全身运动学及椎旁肌激活 控制。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的作用机理。在这项研究中，我们建议1)量化椎旁肌的空间分布 脂肪渗透和由此产生的脂肪图谱与cLBP和退行性IVD病理的关联，2)量化运动 从多域肌肉激活和运动学数据类型控制模式，并与cLBP相关联 症状和PSM FI，以及3)揭示不同PSM FI潜在的生物分子机制 和慢性下腰痛患者的运动控制模式。这项研究是专门为调查不同的原因而设计的 轴性cLBP患者的PSM如何可能被脂肪渗透，以及潜在的残疾 慢性下腰痛患者与PSM-FI相关的功能结局。这项工作将增进我们对 PSM FI与cLBP的临床相关性和致病机制，并为未来使用PSM提供信息 FI作为一种成像生物标志物来优化特定肌肉靶向cLBP疗法的患者选择 改善结果。

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.