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: 8036403
• 负责人: HELENE M LANGEVIN
• 金额: $ 36.44万
• 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/8036403
• 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; 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. PUBLIC HEALTH RELEVANCE: Despite the widespread use of manual and movement-based therapies for the treatment of low back pain (LBP), the mechanisms by which these treatments may promote healing in this condition remain largely unknown. This lack of understanding constrains the development of improved treatments and is an obstacle to the integration of these CAM modalities into the mainstream management of LBP. This study aims to establish a basic mechanism common to manual and movement-based therapies that will strengthen the rationale for these treatments.

描述（由申请人提供）：软组织的拉伸（结缔组织和肌肉）是手动（例如按摩）和基于运动的（例如瑜伽）CAM疗法的重要组成部分，在慢性和再生后疼痛（LBP）的临床试验中已被发现有效。尽管临床试验的证据开始表明这些CAM治疗在慢性下腰痛（LBP）中有效，但这些治疗方法是有益的机制仍然未知。我们假设1）结缔组织（CT）纤维化，伴有神经系统致敏，可以在结合微型损伤和运动限制的猪模型中进行实验产生，以及2）在该猪模型中，结缔组织组织和神经系统的病理学都是可逆的，并且可以通过组织拉伸来清除。该项目将为未来的机械研究奠定阶段，以了解组织在人类中的影响。我们将比较四组迷你猪（每组48头猪，12头猪）随机分配到：1）下背部和骨盆的运动限制为8周，2）PCT微型发作，然后观察8周，然后观察8周，3）PCT微型机械，然后进行8周的运动限制，然后进行8周和4）正常对照。所有猪将使用无线方向传感器进行每周的超声和步态分析（AIM 1）。然后，我们将在由AIM1的结果确定的持续时间内比较两组猪（每组24个猪，每组12头猪）和PCT Microinjoury加运动限制​​，然后进行4周而无需移动限制，在此期间将猪随机分配至1）被动拉伸或2）。对于这两个目的，主要结局措施将是PCT厚度（体内），PCT剪切平面运动（体内），密集的PCT胶原束间距（EX VIVO），PCT型PCT型1 procollagen含量和are骨PCT固体（Ex vivo）。次要结局度量将是步态（体内），贝波尔PCT细胞介导的组织弛豫（EX VIVO），鼻孔PCT神经源性炎症（NGF，IL1-2和TNF-1）和脊髓索P和脊髓索P和CGRP纤维密度的标志。我们建议PCT纤维化和神经系统敏化是导致LBP慢性的病理生理机制的关键组成部分，可以通过组织拉伸逆转。未来的项目将测试这些病理异常的可逆性及其与结缔组织结构和生物力学的非侵入性测量的临床试验中的临床改进的关系。我们的长期目标是利用这种改进的机械理解作为开发LBP理性综合治疗指南的基础，以获得最大的治疗益处。 公共卫生相关性：尽管将手动和基于运动的疗法广泛用于治疗腰痛（LBP），但这些治疗方法可能在这种情况下促进愈合的机制仍然很大程度上尚不清楚。缺乏理解会限制改进治疗的发展，这是将这些CAM模式整合到LBP主流管理中的障碍。这项研究旨在建立一种基于手动和运动疗法共同的基本机制，以加强这些治疗方法的理由。