## 4 Discussion
In the present study, pain begins 4 h after spacer placement, gradually increases, peaks the day after spacer placement, and then subsides [55]. The grades of pain experienced in orthodontic treatment depend on the type of dental movement involved and, particularly, on the pain threshold of each individual [49]. In the present study, there was no significant difference in pain during chewing, which contradicts the literature, revealing that pain is usually aggravated during chewing, forcing the patient to use analgesics [56]. Regarding the adverse effects of the administered drugs, there were no significant differences in the manifestation of heartburn, headaches, and pain when chewing. Acetaminophen can be considered the treatment of choice because it does not cause gastrointestinal ulcers and does not affect the amount of dental movement [57]. This is consistent with our results, as no patients reported heartburn while using this medication. We attributed this finding to the lack of statistically significant differences in the number of patients evaluated, and the level, duration, and direction of the applied force, which may not have been optimal. Despite the cautions taken in sample collection, processing, and storage, the possibility of sample degradation cannot be ruled out. When prescribing analgesics for pain relief in patients after the activation of orthodontic appliances, we must take into account the side effects and the influence they may have on dental movement. The implications of this study are significant for orthodontic practice, as they suggest that pain management with certain analgesics can influence bone remodeling, a critical factor for effective tooth movement during orthodontic treatment. This finding is pivotal as it may lead to a re-evaluation of pain management strategies in orthodontics to avoid compromising treatment efficacy. However, the limitations, including the small sample size and the nature of it being a pilot study, indicate that the results are preliminary. Future research should take several directions. Firstly, there is a highlighted need for more extensive studies to confirm and expand upon these findings, focusing on how different doses and types of analgesics specifically impact bone remodeling and dental movement; this would provide clearer guidance for pain management in orthodontic patients. Additionally, further research into the influence of analgesics on dental movement and bone resorption at the molecular level is suggested; such research is crucial for a better understanding of pain management in orthodontics and its impact on the effectiveness of orthodontic treatment. Conceptualization, J.L.M.-R. and J.R.G.-S.; methodology, S.M.L.-M., S.S.-F., R.R.-M., V.M.d.C.M.-R., Y.I.P.-G. and J.R.G.-S.; software, R.A.B.-G.; formal analysis, J.R.G.-S.; investigation, R.R.-M., Y.I.P. [PERSON], [PERSON] and [PERSON]; writing--original draft, [PERSON], [PERSON],[PERSON] and [PERSON]; writing--review and editing, [PERSON] and [PERSON]; supervision, [PERSON]; project administration, [PERSON] and [PERSON]. All authors have read and agreed to the published version of the manuscript. This research did not receive any external funding. The study adhered to the principles of the Declaration of Helsinki and received approval from the Ethics and Research Committees of Guadalajara University. Additionally, it complied with the Regulations of the General Health Law, obtaining the approval number (CI04820) August 2020, for studies involving human subjects. All participants involved in the study provided informed consent. The data supporting the conclusions of this study are accessible from the corresponding author upon reasonable request. The data are not publicly available due to privacy. This work was supported by the University of Guadalajara's Program for the Improvement of Production Conditions of SNII Members (PROSNI). Special thanks to orthodontists [PERSON] and [PERSON]. The authors declare no conflicts of interest.