Effect of Stretching on Inflammatory Resolution

在急性损伤后或在存在重复创伤时，肌肉骨骼疼痛的持续性是 常见且令人衰弱。组织炎症是急性和慢性阻塞性肺疾病病理生理过程中的重要因素。 慢性过度使用损伤，越来越多的人担心非类固醇抗炎药的使用可能会延缓创伤的完全愈合 此外，还会引起频繁的和潜在的严重副作用。因此，重要的是要 了解并开发可激活自然发生的机制以促进愈合的治疗方法 在不使用药物的情况下，减少伤害，防止慢性肌肉骨骼疼痛。最近有研究表明， 炎症的消退涉及到部分来源于饮食n-3的专门的促消炎介质(SPM) 脂肪酸，我们之前的研究已经开始表明，结缔组织的伸展和 炎症局部消退。在啮齿动物模型中，每天伸展10分钟既减少了急性伸展，也减少了 慢性炎症和炎性病变局部SPM水平升高。此外，伸展的 结缔组织体外可减少中性粒细胞迁移，提高组织浓度。 SPMS，这表明拉伸在结缔组织中具有直接的促进分解的作用。在这个项目中，我们 提出一系列实验来验证这样的假设：1)结缔组织的拉伸促进 局部二十烷类从促炎(白三烯)转变为促拆分(分解素、脂氧素)，减少 中性粒细胞聚集和促进前分辨巨噬细胞的产生；2)非类固醇抗炎药和 缺乏n-3脂肪酸的饮食减少了拉伸诱导的SPM产生，并抑制了拉伸对小鼠的影响 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。我们将用活体啮齿动物来检验这些假说 急性自限和慢性皮下炎症模型，中性粒细胞迁移的体外模型 以及体外成纤维细胞和单核细胞填充的胶原凝胶。 由于目前的局限性，研究拉伸对炎症消退的影响具有重要意义。 以及治疗肌肉骨骼疼痛和炎症的药理方法的副作用。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 回应。如果成功，这个项目将极大地影响对基础知识的理解 与药物治疗、饮食和一系列基于运动的治疗有关的正在发生的愈合机制 伸展运动包括理疗、太极和瑜伽。

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.