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

慢性腰痛患者椎旁肌肉脂肪浸润的机制结构与功能关系

基本信息

批准号：
10660027
负责人：
Jeannie Fern Bailey
金额：
$ 35.53万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-01 至 2028-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10660027
关键词：
3-Dimensional Affect Age Astronauts Atrophic Biomechanics Biometry Biopsy Chronic low back pain Complex Data Deformity Electromyography Exposure to Fatigue Fatty acid glycerol esters Fibrosis Functional disorder Future Gene Expression Genes Health Infiltration Inflammatory Inflammatory Response Injections Intervertebral disc structure Longitudinal Studies Machine Learning Magnetic Resonance Imaging Maps Measurement Methods Molecular Movement Muscle Muscle Development Operative Surgical Procedures Pain management Pathology Pathway Analysis Patient Selection Patients Pattern Phenotype Positioning Attribute Posture Procedures Risk Role Rotation Slipped Disk Space Flight Spatial Distribution Spinal Structure Structure-Activity Relationship Surface Symptoms System Testing Therapeutic Time Tissue Sample Uncertainty Vertebral column Walking Work clinical imaging clinically relevant disability effective therapy functional outcomes imaging biomarker improved improved outcome intervertebral disk degeneration kinematics motor control muscle degeneration muscle regeneration neuromuscular novel novel strategies novel therapeutics pain patient pain symptom prescription opioid prevent rehabilitation strategy response stem cells tool transcriptome wearable sensor technology

项目摘要

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.

项目概要慢性腰痛 (cLBP) 是世界上最严重的使人衰弱的疾病，也是导致腰痛的最常见原因。美国的阿片类药物处方。虽然轴向 cLBP 通常被认为是非特异性和多因素的，但它是经常怀疑脊柱稳定系统功能障碍，包括椎间盘（IVD）和相邻的椎旁肌 (PSM)。由于不确定性，轴性 cLBP 的治疗极具挑战性关于阻碍有效匹配治疗的患者特定因果机制。 IVD变性是通过临床影像很容易理解并经常进行研究。关于 PSM 变性的作用知之甚少，包括萎缩和脂肪浸润 (FI)，这些被认为与 cLBP 有关，尽管现有证据确实表明不提供明确的关联。鉴于量化 FI 的先进 MRI 序列的可用性，现在可以研究 PSM FI 模式，了解其与 cLBP 功能结果的关系患者。目前的工作假设是，退行性 IVD 病理学促进 PSM FI 肌肉的代偿性生物力学反应，试图稳定受影响的脊柱节段加班会导致神经肌肉疲劳和/或直接接触 IVD 产生的促炎因子损害。我们假设 PSM FI 空间分布模式（脂肪图）与 1) 具有显着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，衍生来自患者 PSM 肌肉活检。为了检验这一假设，我们将量化 PSM FI、退行性 IVD 病理学、 40 名中轴 cLBP 受试者和 40 名年龄匹配的受试者的躯干和全身运动学以及椎旁肌激活控制。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 的机制。在本研究中，我们建议 1) 量化椎旁肌的空间分布脂肪浸润并将所得脂肪图与 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，3) 揭示不同 PSM FI 背后的不同潜在生物分子机制 cLBP 患者的运动控制模式。这项研究经过独特设计，旨在调查不同的原因了解 PSM 如何在轴性 cLBP 患者中被脂肪浸润，此外，潜在的致残性 cLBP 患者的功能结果与 PSM FI 相关。这项工作将加深我们对 PSM FI 与 cLBP 的临床相关性和因果机制，并为未来使用 PSM 的工作提供信息 FI 作为成像生物标志物，可优化特定肌肉靶向 cLBP 疗法的患者选择，改善结果。