Connective tissue and nervous system mechanisms of CAM therapies for low back pai

CAM疗法治疗腰痛的结缔组织和神经系统机制

• 批准号: 8433251
• 负责人: HELENE M LANGEVIN
• 金额: $ 37.74万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8433251
• 关键词: Back; Biomechanics; Chronic; Chronic low back pain; Clinical; Clinical Trials; Collagen; Connective Tissue; Connective Tissue Cells; Development; Family suidae; Fiber; Fibrosis; Future; Gait; Goals; Guidelines; Healed; Health; Histocompatibility Testing; Human; Injury; Interleukin-1; Link; Low Back Pain; Mainstreaming; Manuals; Massage; Measurement; Measures; Mediating; Miniature Swine; Modality; Modeling; Motion; Movement; Muscle; Nervous system structure; Neurogenic Inflammation; Outcome Measure; Pathology; Pelvis; Placebos; Plastics; Procollagen; Property; Randomized; Recurrent Low Back Pain; Relaxation; Research Project Grants; Research Proposals; Role; Series; Spinal Cord; Staging; Stretching; Structure; Substance P; TNF gene; Testing; Therapeutic; Thick; Time; Tissues; Translational Research; Ultrasonography; Wireless Technology; Yoga; base; connective tissue development; density; design; effective therapy; gait examination; healing; improved; in vivo; primary outcome; response; secondary outcome; sensor; soft tissue

DESCRIPTION (provided by applicant): Stretching of soft tissue (connective tissue and muscle) is an important component of manual (e.g. massage) and movement-based (e.g. yoga) CAM therapies that have been found to be efficacious in clinical trials of chronic and recurrent low back pain (LBP). Although evidence from clinical trials is beginning to show that these CAM treatments are effective in chronic low back pain (LBP), the mechanisms by which these treatments are beneficial remain unknown. We hypothesize that 1) connective tissue (CT) fibrosis, accompanied by nervous system sensitization, can be produced experimentally in a porcine model combining microinjury and movement restriction and 2) in this porcine model, both connective tissue and nervous system pathologies are reversible and can be ameliorated by tissue stretch. This project will set the stage for a future mechanistic study of the effect of tissue stretch in humans. We will compare four groups of mini-pigs (48 pigs, 12 pigs per group) randomized to: 1) movement restriction of the low back and pelvis for 8 weeks, 2) PCT microinjury followed by observation for 8 weeks, 3) PCT microinjury followed by movement restriction for 8 weeks and 4) normal controls. All pigs will undergo weekly ultrasound and gait analysis using wireless orientation sensors (Aim 1). We will then compare two groups of pigs (24 pigs, 12 pigs per group) all with PCT microinjury plus movement restriction for a duration determined by the results of Aim1, followed by 4 weeks without movement restriction during which pigs will be randomized to 1) passive stretching of the trunk or 2) sham stretching (Aim 2). For both Aims, primary outcome measures will be PCT thickness (in vivo), PCT shear plane motion (in vivo), dense PCT collagen bundle spacing (ex vivo), areolar PCT Type-1 procollagen content and areolar PCT stiffness (ex vivo). Secondary outcome measures will be intersegmental motion during gait (in vivo), areolar PCT cell-mediated tissue relaxation (ex vivo), markers of areolar PCT neurogenic inflammation (NGF, IL1-2 and TNF-1) and spinal cord Substance P and CGRP fiber density. We propose that PCT fibrosis and nervous system sensitization are key component of the pathophysiological mechanism leading to LBP chronicity that can be reversed by tissue stretch. Future projects will test the reversibility of these pathological abnormalities and their relationship to clinical improvement in clinical trials using ultrasound-based non-invasive measures of connective tissue structure and biomechanics. Our long term goal is to use this improved mechanistic understanding as a basis for the development of rational integrative treatment guidelines for LBP for maximum therapeutic benefit.

描述（由申请人提供）：伸展软组织（结缔组织和肌肉）是手动（例如按摩）和基于运动（例如瑜伽）的CAM治疗的重要组成部分，已发现其在慢性和复发性腰痛（LBP）的临床试验中有效。尽管临床试验的证据开始表明这些CAM治疗对慢性腰痛（LBP）有效，但这些治疗有益的机制仍然未知。我们假设：1）结缔组织（CT）纤维化，伴随神经系统致敏，可以在结合微损伤和运动限制的猪模型中通过实验产生; 2）在该猪模型中，结缔组织和神经系统病理都是可逆的，可以通过组织拉伸得到改善。该项目将为未来人体组织拉伸效应的机制研究奠定基础。我们将比较四组小型猪（48只猪，每组12只猪），随机分为：1）下背部和骨盆运动限制8周，2）PCT微损伤后观察8周，3）PCT微损伤后运动限制8周，4）正常对照组。所有猪将使用无线定向传感器每周进行超声和步态分析（Aim 1）。然后，我们将比较两组猪（24只猪，每组12只猪），所有猪均具有PCT微损伤加运动限制，持续时间由目标1的结果确定，随后4周无运动限制，在此期间，猪将随机分为1）躯干被动拉伸或2）假拉伸（目标2）。对于这两个目的，主要结局指标将是PCT厚度（体内）、PCT剪切平面运动（体内）、致密PCT胶原束间距（体外）、乳晕PCT 1型前胶原含量和乳晕PCT硬度（体外）。次要结局指标将是步态期间的节段间运动（体内）、乳晕PCT细胞介导的组织松弛（离体）、乳晕PCT神经源性炎症的标志物（NGF、IL 1 -2和TNF-1）以及脊髓P物质和CGRP纤维密度。我们认为PCT纤维化和神经系统致敏是导致LBP慢性化的病理生理机制的关键组成部分，可以通过组织拉伸逆转。未来的项目将使用基于超声的结缔组织结构和生物力学的非侵入性测量，在临床试验中测试这些病理异常的可逆性及其与临床改善的关系。我们的长期目标是使用这种改进的机制的理解为基础的发展合理的综合治疗指南LBP最大的治疗效益。