## 4 Discussion
Therefore, it is believed that the use of acetaminophen has no effect on dental movement speed [49]. Some information is available on molecular RANK-L expression following analgesic administration in humans. Among the limited studies, [PERSON] et al. compared the effects of ibuprofen and acetaminophen on PGE2 levels in gingival crevicular fluid (GCF) during orthodontic movement. The conclusion suggested that acetaminophen has minimal impact on PGE2 levels, establishing it as a safe and preferred drug for pain relief in patients undergoing orthodontic treatment [28]. According to the results of the present study, a significant increase in RANK-L concentration was observed in the control group, suggesting that ketorolac and acetaminophen decrease RANK-L concentrations. Pain control during the first treatment sessions can increase patient motivation and cooperation [50]. Recent research mentions that there is a rapid release of biochemical markers that cause pain in the first 2 h after the placement of an elastic separator or orthodontic appliance, reaching their maximum expression at 24 h [28; 51]. These results support the findings of the present study since there was a higher release of RANK-L in the control group at 24 h. Furthermore, in 2006, [PERSON] et al. investigated the dynamics of RANK-L and OPG levels in GCF during canine retraction without administering drugs and in an acetaminophen group. They included both in vivo and in vitro analysis using ELISA to quantify the cytokines. The findings suggest that changes in RANK-L and OPG are involved in bone resorption in response to compression force, which may have implications for the regulation of tooth movement in orthodontic treatments [27]. These results coincide with the present study: RANK-L expression was increased at 24 h in the control and acetaminophen groups. As mentioned above, the age range of the patients included in this study was 18 to 27 years; these are considered young patients. In 2006, [PERSON] et al. conducted a comparative study on the levels of RANK-L and OPG in the GCF during OTM in juvenile and adult patients. The study involved 15 juveniles and 15 adults, with the collection of gingival crevicular fluid (GCF) samples at different time points after the application of a retraction force. Findings indicated that tooth movement was greater in juveniles than in adults after 168 h, similar to the present study. Moreover, there was an increase in RANK-L levels and a decrease in OPG levels in the GCF of both groups. The RANKL/OPG ratio was lower in adult patients compared to juveniles, suggesting that the age-related decrease in tooth movement might be linked to a reduction in the RANK-L/OPG ratio in the GCF during the initial stages of OTM [52]. The results of the present work indicate that dental movement measured through the space generated between the premolar and the upper molar in the different groups was not significant. On the contrary, [PERSON] et al. compared separation and associated pain. This study concludes that the larger the interdental space, the greater the pain at 24 h [53]. This differs from the present study, in which we obtained a negative correlation between space and pain, indicating that the larger the interproximal space, the less pain the patient experiences. In addition to this, [PERSON] et al. showed that the gap is created after 24 h of stimulation and that it only needs to be 0.16 mm, as this is the standard orthodontic band size [53]. However, the average spacing obtained in the present study was 0.28 mm. It is known that only 0.025 mm is required for band placement [54]. There is no correlation between the amount of RANK-L and the space obtained, which differs from what was expected. [PERSON] and [PERSON] suggest that changes in RANK-L are involved in bone resorption in response to compression force, which may have implications for the regulation of tooth movement in orthodontic treatments [27; 52].