Effect of Stretching on Inflammatory Resolution

急性损伤后或反复创伤后肌肉骨骼疼痛的持续性， 常见且令人衰弱。组织的炎症是急性和慢性炎症的病理生理学中的重要因素。 慢性过度使用损伤，并且越来越多的人担心使用NSAID可能会延迟 此外，它还导致频繁和潜在的严重副作用。因此必须 了解并开发可能激活自然发生机制以增强愈合的治疗方法 在不使用药物的情况下，预防慢性肌肉骨骼疼痛。最近的研究表明， 炎症的消退涉及部分来源于饮食n-3的特化促消退介质（SPMs） 脂肪酸，我们以前的研究已经开始显示结缔组织的拉伸和 炎症局部消退。在啮齿动物模型中，每天拉伸10分钟， 慢性炎症和炎性病变中SPM的局部水平增加。此外，拉伸 离体结缔组织减少了中性粒细胞的迁移，并提高了组织中 SPM，表明拉伸在结缔组织内具有直接的促分辨率效应。本课题 提出一系列实验来检验以下假设：1）结缔组织的伸展促进了 局部类花生酸从促炎症（白细胞三烯）转变为促消退（消退素，脂氧素）， 中性粒细胞积聚并增强促消退巨噬细胞的产生; 2）NSAID和 缺乏n-3脂肪酸的饮食减少了牵张诱导的SPM产生，并抑制了牵张对 炎症的自然消退和3）拉伸在结缔组织内具有直接的促消退作用， 涉及成纤维细胞-基质相互作用机制的组织。我们将使用体内啮齿动物来检验这些假设 急性自限性和慢性皮下炎症模型，中性粒细胞迁移的离体模型 以及体外成纤维细胞和单核细胞聚集的胶原凝胶。 由于目前的局限性，研究拉伸对炎症消退的影响是重要的 以及治疗肌肉骨骼疼痛和炎症的药理学方法的副作用。我们的研究是 在研究连接结缔组织、身体运动和免疫的新机制方面具有创新性 应答如果成功，这个项目将大大影响对基本原理的理解， 发生与药物治疗、饮食和一系列基于运动的治疗相关的愈合机制 包括理疗、太极和瑜伽在内的伸展运动。

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.