Manipulation of the Fascial System Applied During Acute Inflammation of the Connective Tissue of the Thoracolumbar Region Affects Transforming Growth Factor-β1 and Interleukin-4 Levels: Experimental Study in Mice

Maria Elisa Duarte França,Larissa Sinhorim,Verônica Vargas Horewicz,Robert Schleip,Nicolas A M M Machado-Pereira,Daniel Fernandes Martins,Gabriel Melo De Souza,Gilmar Moraes Santos

doi:10.3389/fphys.2020.587373

Abstract

Fascia can become rigid and assume a fibrotic pattern due to inflammatory processes. Manipulation of the fascial system (MFS), manual technique targeting connective tissues, is commonly used in clinical practice in pain management. We aimed to verify MFS effects on the connective tissue inflammatory changes in mice. Swiss Mus musculus male mice (n = 44) were distributed into groups: carrageenan without treatment (Car, n = 11), carrageenan with MFS (Car + MFS, n = 12), saline without treatment (n = 10), and saline with MFS (saline + MFS, n = 11). Interleukin 4 (IL-4), IL-6, tumor necrosis factor (TNF), transforming growth factor β1 (TGF-β1), and monocyte chemoattractant protein 1 (MCP-1) levels were verified by enzyme-linked immunosorbent assay. Neutrophil (Ly-6G), macrophage (F4/80), and nitric oxide synthase 2 (NOS-2) were identified using Western blot. The MFS protocol was applied from the first to the third day after inflammation of the connective tissue of the thoracolumbar region. There was a significant MFS effect on IL-4 (p = 0.02) and TGF-β1 (p = 0.04), without increasing MCP-1, TNF, and IL-6 levels (p > 0.05) on thoracolumbar region from Car + MFS, in comparison with saline. Ly-6G in Car + MFS presented lower levels when compared with saline (p = 0.003) or saline + MFS (0.003). NOS-2 levels were lower in Car + MFS than in saline + MFS (p = 0.0195) or saline (p = 0.003). MFS may have an anti-inflammatory effect, based on TGF-β1 and IL-4. IL-4 may have inhibited neutrophil migration. Lower levels of NOS-2 may be linked to the lack of macrophages, which are responsible for NOS-2 expression.

Highlights

Fascia is a connective tissue composed of collagen fibers (Willard et al, 2012) that enables sliding between surfaces (Langevin et al, 2011); it is known that it has an important role in locomotion withal, as it acts as a transmission force mechanism between adjacent synergist and antagonistic muscles (Garfin et al, 1981)
In the present study, using a translational research perspective, we investigated the effects of Manipulation of the fascial system (MFS) on the connective tissue of the thoracolumbar in acute inflammation using a carrageenaninduced inflammation mice model
In the connective tissue of the thoracolumbar region, significantly higher levels of transforming growth factor β1 (TGF-β1) (p = 0.047) and Interleukin 4 (IL-4) (p = 0.026) were found in the carrageenan group (Car) + MFS group when compared with the saline group (Figures 2A,B, respectively)

Summary

Introduction

Fascia is a connective tissue composed of collagen fibers (Willard et al, 2012) that enables sliding between surfaces (Langevin et al, 2011); it is known that it has an important role in locomotion withal, as it acts as a transmission force mechanism between adjacent synergist and antagonistic muscles (Garfin et al, 1981). Thereby, the stiffness of the connective tissue may affect sliding between surfaces, once the adjacent connective tissue layers are relevant in structures, such as the connective tissue of the thoracolumbar region, in which the density layers correspond to aponeuroses of muscles with different traction directions: longitudinal (for latissimus dorsi, posterior serratus, and erector spinae) vs transversal (for internal/external obliques and latissimus dorsi) (Langevin et al, 2011) If sliding between these tissues is compromised, and the fascia biomechanical properties are changed, it may contribute to musculoskeletal pain (Klingler et al, 2014)

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