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Effect of Stretching on Inflammatory Resolution

拉伸对炎症消退的影响

基本信息

批准号：
9315093
负责人：
HELENE M LANGEVIN
金额：
$ 50.97万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9315093
关键词：
Acute Address Adverse effects Anti-Inflammatory Agents Anti-inflammatory Attenuated Caring Carrageenan Cells Chronic Collagen Connective Tissue Cumulative Trauma Disorders Cyclooxygenase Inhibitors Data Diet Dose Drug usage Eicosanoids Exercise Female Fibroblasts Flow Cytometry Functional disorder Gap Junctions Gel Hour Ibuprofen Immune response Immune system In Vitro Inflammation Inflammatory Injection of therapeutic agent Injury Investigation Laboratories Lead Lesion Lifting Link Lipoxins Mediator of activation protein Modeling Morbidity - disease rate Movement Musculoskeletal Pain Musculoskeletal System N-3 polyunsaturated fatty acid Omega-3 Fatty Acids Pain Patients Pharmaceutical Preparations Pharmacology Pharmacotherapy Physical activity Physical therapy Process Production Public Health Rattus Research Resolution Rodent Model Safety Series Societies Sports Stretching Subcutaneous Tissue Tai Ji Testing Therapeutic Time Tissues Trauma Work Yoga base body system cost experimental study healing in vivo indexing inflammatory marker innovation lipid mediator macrophage male migration monocyte neutrophil novel prevent reduce symptoms response subcutaneous tool

项目摘要

The persistence of musculoskeletal pain after an acute injury, or in the presence of repetitive trauma, is common and debilitating. Inflammation of tissues is an important factor in the pathophysiology of acute and chronic overuse injuries, and there is growing concern that the use of NSAIDs may retard the full healing of tissues in addition to causing frequent and potentially serious side effects. It is therefore important to understand and develop treatments that may activate naturally occurring mechanisms to enhance the healing of injuries and prevent chronic musculoskeletal pain without the use of drugs. It was recently shown that the resolution of inflammation involves specialized pro-resolving mediators (SPMs) derived in part from dietary n-3 fatty acids, and our previous studies have begun to show a link between stretching of connective tissue and local resolution of inflammation. In rodent models, daily stretching for 10 minutes decreased both acute and chronic inflammation and increased local levels of SPMs in the inflammatory lesion. Furthermore, stretching of connective tissue ex vivo decreased the migration of neutrophils and enhanced the tissue concentration of SPMs, suggesting that stretching has direct pro-resolution effects within connective tissue. In this project, we propose a series of experiments testing the hypotheses that: 1) stretching of connective tissue promotes a local eicosanoid shift from pro-inflammation (leukotrietenes) to pro-resolution (resolvins, lipoxins), reduces neutrophil accumulation and enhances the production of pro-resolution macrophages; 2) both NSAIDs and a diet deficient in n-3 fatty acids decrease stretch-induced SPM production and inhibit the effect of stretching on the natural resolution of inflammation and 3) stretching has direct pro-resolution effects within connective tissue that involve fibroblast-matrix interaction mechanisms. We will test these hypotheses using in vivo rodent models of acute self-limiting and chronic subcutaneous inflammation, an ex vivo model of neutrophil migration and in vitro fibroblast- and monocyte-populated collagen gels. Investigating the effect of stretching on inflammation resolution is significant because of the current limitations and side effects of pharmacological approaches to treat musculoskeletal pain and inflammation. Our study is innovative in its investigation of novel mechanisms linking connective tissue, body movement and immune responses. If successful, this project will significantly impact the understanding of fundamental, naturally occurring healing mechanisms relevant to pharmacotherapy, diet and a range of movement-based therapies with a stretching component including physical therapy, Tai Chi and yoga.

急性损伤后持续的肌肉骨骼疼痛，或在存在重复性创伤，是