# The Use of Ibuprofen Arginate in Pain Management Following Third Molar Surgery--A Scoping Review
## 4 Discussion
When administered at nanomolar physiological concentrations, nitric oxide exhibits protective antiapoptotic effects [36; 37; 38; 39; 40], including on epithelial cells of the gastrointestinal tract [41; 42], increases mucin formation, promotes the synthesis of prostaglandamins E2 and gastrin, and enhances the effects of prostacyclin on gastric epithelial cells [43; 44; 45; 46; 47]. Furthermore, nitric oxide may boost blood flow in the gastric mucosa and promote ulcer healing due to its vasodilatory and angiogenic properties [48; 49; 50]. These biological effects may counteract the gastrointestinal damage caused by ibuprofen [35]. Other authors have investigated substances that, when combined with ibuprofen, provide faster pain relief. The review of [PERSON] et al. (2014) shows that maximum ibuprofen concentrations with fast-acting formulations occurred before the 50 min mark (20-40 min after dosing for arginine, lysine, and sodium salts, and 30-50 min after dosing for liquid-filled soft capsules). Conventional ibuprofen took about 90-120 min. Overall, fast-acting formulations were found to be slightly more effective than standard ibuprofen, especially in terms of achieving 50% of the maximum total pain relief (P50% maxTOTPAR). This was particularly noticeable with the 200 mg dose of ibuprofen arginine, where fewer patients needed to take additional medication compared to those on standard formulations. The 200 mg dose of ibuprofen arginine showed the greatest improvement in pain relief compared to the same dose of standard ibuprofen, highlighting the benefit of the fast-acting formulation [51]. Another studied combination involves ibuprofen and caffeine, which has been shown to enhance analgesic efficacy and reduce the time to the onset of pain relief. In the study of [PERSON] et al. (1991), ibuprofen 200 mg with caffeine consistently demonstrated higher PID scores than ibuprofen 200 mg alone at each hour mark, suggesting that caffeine enhanced the analgesic effect of ibuprofen, which was particularly notable at the 2 and 3 h mark. The results of this study were that ibuprofen 200 mg had a PID of 1.00 and ibuprofen 200 mg plus caffeine had a PID of 1.25 after 2 h; meanwhile, ibuprofen 200 mg had a PID of 0.98 and ibuprofen 200 mg plus caffeine had a PID of 1.36 after 3 h. A 200 mg ibuprofen dose was considered in the above study for both cases. [PERSON] et al. (2002) showed PIDs at 2 h of 2.8 \(\pm\) 1.3 and 2.6 \(\pm\) 1.4 at 3 h [31], while [PERSON] et al. (2002) presented PIDs of 1.3 \(\pm\) 0.9 and 1.1 \(\pm\) 1.1, respectively, after 2 and 3 h [28], and [PERSON] et al. (2002) showed PIDs of 0.4 \(\pm\) 1 at 2 h and -0.1 \(\pm\) 1 at 3 h [32]. Ibuprofen arginine, based on the studies of [PERSON] et al. (2002) [31] and [PERSON] et al. (2002) [28], shows higher PID scores, suggesting superior pain relief properties compared to ibuprofen with caffeine. Only [PERSON] et al. (2002) [32] reported lower scores for ibuprofen arginine compared to ibuprofen plus caffeine. However, it must be pointed out that, in recent years, some new possible medications have been proposed to limit postoperative pain and also prevent complications after this type of extractions [52; 53].