## 4 Discussion
Furthermore, the authors observed an increase of matrix metalloproteinase 2 (MMP-2) concentration in saliva in the laser group. They suggested that this increase may have contributed to the reduction in the severity of OM, where MMP subtypes are implicated in both pro- and anti-inflammatory pathways and play a critical role in tissue remodeling processes [32]. The mechanism of the analgesic effect of PBM has not been fully clarified yet. It is believed that the analgesic effect results from the neurophysiological effects (e.g., the release of endogenous opioids), the local circulatory, angiogenic and anti-inflammatory effects [22]. Some authors have suggested that the reduction in prostaglandin E2 (PGE-2), cyclooxygenase-2 (COX-2) expression, and plasminogen activator after PBM application might also be involved [22; 35]. Recently, the Mucositis study group of MASCC/ISOO carried out a systematic review to update their evidence-based clinical practice guidelines for the use of PBM as a modality for managing OM. The authors observed an inconsistency and diversity in the laser parameters and PBM schedules, including the starting time, the total duration, and the number of sessions per week. They suggested specific settings for PBM for the prevention of OM in patients undergoing HSCT. These specific settings were based on randomized clinical trials with a high level of evidence. The authors believe that these specific PBM settings would be changed in the future based on a better understanding of the precise roles of each PBM parameter [25]. In the literature, the wavelengths used for OM ranged from 630 nm to 970 nm [27]. In our study, a double diode laser with two different wavelengths of 650 nm (red range) and 910 nm (infrared range) was employed using the laser light guide red 650 nm and the 904-910 nm. [PERSON] et al. carried out a study to compare two different wavelengths (650 nm and 780 nm) for the prevention of OM and pain relief. The authors found that the red range lasers (650 nm) were more effective in preventing OM lesions, while infrared lasers (780 nm) were more effective for the relief of pain [33]. The total energy deposited in the oral cavity per each PBM session should be considered as one of the most important PBM parameters for OM [22]. It was noticed that some studies with similar outcomes had the same total energy but they differed with respect to the other laser parameters [22; 36]. In our study, the total irradiation energy per session was 40 J. This value increased due to the additional application of PBM on the developed OM lesions. The timing of the start of PBM differed among previous studies. Some studies started the PBM prior to, or with the start of conditioning regimens; in others, the PBM was started on, or after the day of transplantation [1; 25; 27; 28]. In our study, the PBM was started one day before the start of the conditioning regimen. [PERSON] et al. believe that the lack of improvement in OM measurements in their study was due to the late start of PBM (the day of transplantation). They speculated that this was because the initiation phase of OM occurs with the start of the conditioning regimen; therefore, if the decrease in the severity of OM by PBM is due to a decrease in the amplification of the inflammatory process, the early start of PBM may lead to more favorable outcomes [1]. The total duration of the PBM protocol is considered to be an influencing factor on studies' outcomes. [PERSON] et al. compared the outcomes of their study with other studies with similar laser parameters. They found that studies with a shorter duration of the laser treatment did not show the same positive results. The mean duration of the PBM was 22 days [37]. The mean duration of PBM in our study was 21 days with an average of 16 PBM sessions. The onset of OM has been reported to be 5-10 days from the start of the conditioning regimen with a duration of 1-2 weeks [38]. In our study, the mean duration of OM in the PG was 4.7 days, while in the CG the mean duration was 15 days.