Discusión sobre el objetivo: “Analizar la viabilidad de una propuesta que modifique los

Appropriate mechanical loading stimulates protein synthesis at the cellular level, promoting tissue repair and remodelling (Wang et al., 2012) as well as cell proliferation and migration in wound healing, by sensitizing fibroblasts to nitric oxide (Cao et al., 2013b)

During manual fascial techniques, the operator may feel various tissue responses to the applied load that are described as ‘resistance’ or ‘give’ to the stretch. Interestingly, the

mechanical loading of fascia causes changes through activation of fibroblast response and the different receptors present in the fascial tissue, leading to modulation of myofascial contraction (Hicks et al., 2014).

The existence of a-smooth muscle actin (ASMA) in human fascia was discussed in an article by Schleip et al. in 2005 and hypothesised that fascia can undergo spontaneous contractions to create a pre-stress in the collagen scaffold, while no quantitative immunohistochemical examination has yet been published for cells containing ASMA in normal fascial sheets, the existence of cells resembling smooth muscle cells was accidentally discovered by Staubesand (1997) in normal crural fascia and has been documented with electron microscopy. Since the crural fascia has a similar morphology to the lumbar fascia or to the muscular epimysial envelopes, it seems reasonable to extrapolate that the crural fascia is not the only fascial sheet with this property (Schleip et al., 2005). It, therefore, can be cautiously assumed that contractile cells are probably also present in other dense human fascial sheets as have already been found in tendons, ligaments and in the crural fascia.

Masood and Naylor (1994 a, b; 1995) reported that superficial and deep lumbar fascia from rats as well as from guinea pigs contracted in response to in-vitro application of the myofibroblast stimulant mepyramine as well as to the smooth muscle agonists adenosine and angiotensine II. Contractions started within several minutes and were in a dose dependent, reproducible and reversible manner. The smooth muscle relaxing substances nifedipine and EDTA (ethylene diamine tetra acetic acid) as well as the microtubule disrupting substance cytochalasin-D exhibited a relaxing effect. A relaxing response in porcine lumbar fascia to the substance glyceryltrinitrate (a nitric oxide donor and smooth muscle relaxant) has been reported by Schleip et al. (2004). Malata et al. (1994) found that mepyramine-induced contractions in rat subcutaneous fascia were enhanced by previous incubation with heparin. Using an immunohistochemical analysis of 39 tissue samples from the thoracolumbar fascia of

11 human donors (ages 19–76 years), Schleip et al. (2004) demonstrated the widespread presence of myofibroblasts in all samples, with an average density of 79 cells/mm2 _{in this} longitudinal sections. In-vitro experiments with human lumbar fascia by Yahia et al. (1993) reported that with a tissue strip of 1.5 mm x1.0 mm x 30 mm, the maximal measured force increase during an isometric stretch was 1.5 N. If we hypothetically apply the same force ratio to whole fascial sheets in the human body, it seems clear that such fascial contractions could have substantial biomechanical influences (Schleip et al., 2006).

Cao et al (2013) conducted an in-vitro scratch wound strain model analysis to determine the effects of modeled myofascial release on fibroblast wound healing and to investigate the potential role of nitric oxide (NO) in mediating these responses. They found that fibroblasts that received repetitive motion strain (RMS) resulted in reduced wound closure rates (vs nonstrain, P<.05), which were partially attenuated by a single dose of MFR. Fibroblasts and myofibroblasts are both highly responsive to magnitude (Cao et al., 2013; Hicks et al., 2014), direction, frequency and duration (Standley & Meltzer, 2008) of a therapeutic load and can regulate cell activity, proliferation or apoptosis (Meltzer et al., 2010), mainly by influencing ion conductance, gene expression and secretion of inflammatory mediators. In particular, the secretion of IL-6 and IL-1 by fibroblasts under equibiaxial stretch can exert powerful pro or anti-inflammatory responses, potentially leading towards beneficial or detrimental matrix remodelling and cell behaviour (Tsuzaki et al., 2003). A concomitant autocrine and paracrine release of ATP may also serve as a negative feedback mechanism to limit activation of destructive pathways (Tsuzaki et al., 2003) and all of these factors may influence the clinical efficacy of fascial treatment.

The fascial tissue may respond better to balanced and sustained stretch rather than intermittent and unequal loads, including apoptotic rate (Meltzer et al., 2010).The force and

duration of tension applied may also be relevant. It has been shown that high magnitude (therapeutic) load (from 9% to 12% elongation) can produce an upregulation of ECM proteins while increasing magnitude and duration (one to five minutes) loads induce cytokine and growth factors secretions (Cao et al., 2013). These results are consistent with those obtained by Yang et al. (2005) where large-magnitude loads caused pro-inflammatory responses and cyclic (0.5 Hz per 4 h), uniaxial and small-magnitude stretching produced anti-inflammatory reactions in human tendon fibroblasts. Similarly, brief, moderate amplitude (20-30% strain), static stretching of connective tissue in-vivo and ex-vivo has been shown to decrease TGF- b1and collagen synthesis, thus preventing soft tissue adhesions (Bouffard et al., 2008).

In conclusion, brief, light/moderate, balanced, static or slow cyclic strains appropriately applied to fascia may be sensed at the cellular level and transduced in normalizing tissue structure and function (Tozzi 2015b).

The therapeutic loads applied differently with respect to tissue tension (that presumably corresponds to cell orientation) may produce different cell and tissue responses. Finally, secretion of IL-6 was significantly induced by 15 min of cyclic biaxial mechanical stretching after 4 and 8 h in human tendon fibroblasts, suggesting that inflammatory reactions following manual intervention may be partially caused by IL-6 secretion (Skutek et al., 2001).