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

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.

Potential Nociceptive Role of the Thoracolumbar Fascia: A Scope Review Involving In Vivo and Ex Vivo Studies

“…In this sense, preclinical studies that record the results immediately after (or shortly thereafter) the delivery of fascial manipulation, long-term or longitudinal studies, and studies that investigate the physiological impact of different fascial manipulation dosage are needed. As in the study of França et al, 2020 [ 74 ], preclinical studies are just beginning to recognize and demonstrate that analgesic modulation related to fascial manipulation involves complex mechanistic interactions. Thus, preclinical studies that investigate endogenous neurological systems such as endogenous opioids [ 75 ], endocannabinoids [ 76 ], adenosinergic system [ 77 ], and/or neuroimmune contributions [ 74 , 78 ] are needed, and these effects may require that certain fascial manipulation dosage thresholds be achieved.…”

Potential Nociceptive Role of the Thoracolumbar Fascia: A Scope Review Involving in Vivo and Ex Vivo Studies

“…In this sense, preclinical studies that record the results immediately after (or shortly thereafter) the delivery of fascial manipulation, long-term or longitudinal studies are needed, as well as studies that investigate the physiological impact of various of fascial manipulation dosage. As in the França et al, 2020 [70] study, preclinical studies are just beginning to recognize and demonstrate that analgesic modulation related to fascial manipulation involves complex mechanistic interactions. Thus, preclinical studies that investigate endogenous neurological systems, such as: endogenous opioids [71], endocannabinoids [72], adenosinergic system [73], and/or neuroimmune contributions [70,74] are needed, and these effects may require certain fascial manipulation dosage thresholds be achieved.…”

“…As in the França et al, 2020 [70] study, preclinical studies are just beginning to recognize and demonstrate that analgesic modulation related to fascial manipulation involves complex mechanistic interactions. Thus, preclinical studies that investigate endogenous neurological systems, such as: endogenous opioids [71], endocannabinoids [72], adenosinergic system [73], and/or neuroimmune contributions [70,74] are needed, and these effects may require certain fascial manipulation dosage thresholds be achieved. Preclinical studies investigating the effects of fascial manipulation on: gene expression, neurotransmitter / neuropeptide / cytokine release, mechanosensitive ion channel activation, neuroimmune response, global cortical / spinal circuit connectivity and descending inhibition [73], are needed to advance the manual therapy field and deepen our understanding of fascial manipulation.…”

Fibroblasts as confederates of the immune system

“…For example, manipulation of the fascia system by compressing and stretching the subcutaneous fascia is commonly used by physiotherapists to resolve inflammation and manage pain. In a fascia inflammation‐induced mouse model, manipulation of the fascia system practices reduced neutrophil counts and increased levels of interleukin 4 and transforming growth factor‐beta (TGF‐beta), pointing to an anti‐inflammatory effect by modulating fascia connective tissue biomechanics 77 . Future work in this area will reveal the clinical relevance of how changing fascia tissue biomechanics can affect its immunological activity and the pivotal interactions between stromal and immune populations, to support wound repair and regeneration (Figure 3).…”