Effect of Stretching on Inflammatory Resolution

急性损伤后或重复性创伤后肌肉骨骼疼痛持续存在， 常见且令人衰弱。组织炎症是急性和慢性疾病病理生理学的重要因素。 慢性过度使用损伤，人们越来越担心使用非甾体抗炎药可能会延缓损伤的完全愈合 除了引起频繁且潜在严重的副作用之外，因此，重要的是 了解并开发可以激活自然发生机制以增强愈合的治疗方法 无需使用药物即可减少受伤并预防慢性肌肉骨骼疼痛。最近显示， 炎症的消退涉及部分源自膳食 n-3 的专门促消退介质 (SPM) 脂肪酸，我们之前的研究已经开始表明结缔组织的拉伸和 炎症局部消退。在啮齿类动物模型中，每天拉伸 10 分钟，急性和 慢性炎症和炎性病变中局部 SPM 水平升高。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浓度 SPM，表明拉伸在结缔组织内具有直接的促消退作用。在这个项目中，我们 提出一系列实验来测试以下假设：1）结缔组织的拉伸促进 局部类二十烷酸从促炎症（白三烯）转变为促消退（消退素、脂氧素），减少 中性粒细胞积累并增强促消退巨噬细胞的产生； 2) NSAIDs 和 饮食中缺乏 n-3 脂肪酸会降低拉伸诱导的 SPM 产生，并抑制拉伸对身体的影响 炎症的自然消退，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测试这些假设 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物方法的副作用。我们的研究是 对连接结缔组织、身体运动和免疫的新机制的研究具有创新性 回应。如果成功，这个项目将极大地影响对基本原理的理解，自然 与药物治疗、饮食和一系列基于运动的疗法相关的愈合机制 包括物理治疗、太极拳和瑜伽等伸展运动。

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.