## 4 Discussion
Myofascali pain is a complex musculoskeletal disorder characterized by the presence of trigger points, defined as hyperirritable spots within taut bands of skeletal muscle that are painful upon compression [48], characterized by a higher concentrations of protons, bradykinin, calcitonin gene-related peptide, substance P, tumour necrosis factor-a, interleukin-1b, serotonin, and norepinephrine [49]. It has been observed that the masseter and temporalis muscles are the muscles most frequently involved in active trigger points in patients with TMD of myofascali origin [50]. It is important to highlight that, without intervention, the pain could become chronic determining a restriction of the range of motion [51]. The ESWT is a mechanical (acoustic) wave with a low-frequency pressure that propagates rapidly and focally [23]. The rapid growth of rESWT in recent years has positioned it as an alternative to focal ESWT, because unlike focal shock waves, rESWT waves have linear pressure, low energy values, short duration of the rise time, and most of all a radial propagation [25]. These waves are characterized by a slow growing pressure that takes up to 5 us to reach 1-10 bar (0.1-1.0 MPa); moreover and is absorbed at a depth of up to 3 cm, with a typically dispersed (unfocused) beam shape [52]. The mechanism of action of the rESWT on musculoskeletal disorders has been investigated in animal studies. The beneficial effect of shock waves might be associated with micro-destruction, which is likely to result in micro-tears of non-vascularized or scantily vascularized tissues, and thus stimulate the revascularization by the local release of growth factors and mobilization of stem cells, leading to increased blood supply to the tissue [53]. Studies explored the effects of rESWT showing that the application of shock waves could generate the ingrowth of neovascularization through the up-regulation of angiogenic and osteogenic growth factors (e.g., endothelial nitric oxide synthase, vessel endothelial growth factor, proliferating cell nuclear antigen, bone morphogenetic-2, and osteoclast) [54,55]. Moreover, previous studies have suggested that these mechanisms also play a role in reducing the muscle tone for spasticity [24] and that the rESWT may generate an analgesic effect during the treatment that blocks the activation and transmission of pain signals by non-invasive stimulation of cell membranes and nerve endings [25,53]. The clinical effects of rESWT in patients with musculoskeletal disorders have been explored in the recent years [56, 57, 58], and it seems that this therapy could have a significant influence on the reduction of pain and on the improvement of the general functional state. Results of the present study showed that the VAS scores of both groups declined after therapy, and that the decrease was greater in the study group. The significant increased mean values of POC MM that were obtained in rESWT group might indicate a low asymmetry between the right and left muscle pairs and balanced contractile activity [59]. Indeed, a measure of the predominance of the right or left masseter in the posterior teeth contacts provide an index of performance symmetry [46]. The improvement in POC MM of the rESWT group at the end of treatment could justify the improvements at 24 weeks in the significant difference in anterior-posterior BAR between the two groups. In this scenario, the significant pain reduction at the end of the treatment provides early lateral stability, which results in late anterior-posterior stability. We are aware that the present pilot RCT has a main limitation of small sample size, albeit we retain that these findings might report a first proof of this novel intervention in the clinical management of muscle-related TMD. Moreover, the impact of the COVID-19 pandemic might have influenced the follow-up period that could have lasted more to highlight the long-term effects of this intervention.