Exploring the effect of stretching in the resolution of Connective tissue inflammation

National Institute Of Dental & Craniofacial Research

Investigators

Abstract

"Non-specific" musculoskeletal pain involving a wide variety of anatomical areas (temporomandibular, neck, back, extremities) is a major public health problem worldwide that affects quality of life and productivity and is routinely treated with anti-inflammatory drugs. However, there is growing concern that these medications may retard the healing of tissues, in addition to causing serious side effects in multiple organ systems. Therefore developing alternatives to anti-inflammatory medications is a priority. Stretching is an important component of physical therapy and a variety of traditional movement-based practices such as yoga and Tai Chi that have been shown to ameliorate symptoms and decrease systemic inflammatory markers in patients with musculoskeletal pain. Our previous studies in rodents have demonstrated that daily stretching decreases both acute and chronic inflammation. Furthermore, stretching of connective tissue ex vivo decreased the migration of inflammatory cells such as neutrophils, and enhanced the production of lipid-derived specialized pro-resolving mediators (SPMs). In this study we aimed to explore further the effects of stretching at the cellular/molecular level, in a mouse carrageenan-inflammation model. Stretching for 10 minutes twice a day reduced inflammation, increased the production of pro-resolving mediator pathway intermediate 17-HDHA at 48h post carrageenan injection, and decreased both pro-resolving and pro-inflammatory mediators (e.g., PGE2 and PGD2) at 96h. ScRNAseq analysis of inflammatory lesions at 96h showed that stretching increased the expression of both pro-inflammatory (Nos2) and pro-resolution (Arg1) genes in M1 and M2 macrophages at 96 hours. An intercellular communication analysis predicted specific ligand-receptor interactions orchestrated by neutrophils and M2a macrophages, suggesting a continuous neutrophil presence recruiting immune cells such as activated macrophages to contain the antigen while promoting resolution and preserving tissue homeostasis. A manuscript has been submitted on these fundings to the Journal of Cellular Physiology and is under review.