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). Macrophages are another important cell population that play a key role in inflammation, because they ultimately contribute to the resolution of inflammation. In this study we will use high resolution 3D ultrasound to measure the size of inflammatory lesions. We are using immunofluorescence to explore the macrophage populations surrounding the carrageenan lesions from stretched and non-stretched animals. Our preliminary data suggest that although stretching is reducing the size of the inflammation by promoting resolution, there is still activation of inflammatory components since the antigen persist in the tissue. Therefore, we hypothesized that the populations of macrophages in the center of the inflammatory lesions, would be inflammatory (INOS+), whereas macrophages in the outer layers will be anti-inflammatory type (Arginase+), which will contribute to reduce the size of the inflammation. Using immunohistochemistry, we have observed a spatial distribution of macrophages that is consistent with, although not confirmatory, of this hypothesis. We are now using Single cell RNA sequence (scRNAseq) to further characterize the cell populations in the inflammatory lesions and how these are impacted by the mechanical intervention, which contributes to understanding the mechanism of stretching promoting resolution of inflammation.