Impacted third molars are extracted for both prophylactic and therapeutic purposes, as they may cause pain, infection, caries in adjacent teeth, root resorption, cyst formation, or tumor growth. Therefore, third molar surgery is one of the minor procedures frequently used in routine oral surgery practice. Due to the traumatic nature of the operation, complications such as an inflammatory reaction of the tissue, discomfort, edema, and trismus are inevitable afterward1, 2, 3. These complications can compromise patients' quality of life after the extraction of these teeth. Additionally, it can occasionally be challenging for surgeons to manage these complications. Various factors contribute to the development of pain, but the majority are related to the inflammatory process arising from surgical trauma. Controlling this inflammatory process can reduce the severity of pain4,5. Opioids, local anesthetics, and nonsteroidal anti-inflammatory drugs (NSAIDs) are the medications generally preferred as pain relievers following third molar surgery6,7. NSAIDs, by inhibiting cyclooxygenase, reduce pain, trismus, and edema through the prevention of prostaglandin production8.

The preemptive analgesia protocol is one of the many approaches used to alleviate postoperative pain9. This method involves administering analgesic medicine to patients ahead of painful stimuli, especially in surgery-related tissue injuries, to reduce their postoperative pain10. Numerous studies have reported that prophylactic analgesia, administered before the development of pain, improves postoperative outcomes. Consequently, the preemptive analgesia method is now widely preferred in dentistry and medicine to prevent postoperative pain11, 12, 13. Preemptive analgesia is achieved using drugs such as local anesthetics, opioids, and NSAIDs. However, acid NSAIDs such as flurbiprofen, diclofenac, zaltoprofen, loxoprofen, and ibuprofen are typically used in preemptive analgesia studies14.

Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has a regulating influence on central sensitization and has been used as an anesthetic agent for over 40 years15. It is well known that administering ketamine intravenously has an anesthetic effect at high levels and an analgesic effect at low levels. A noticeable analgesic effect is achieved by administering a low dose (0.1-0.5 mg/kg) of ketamine to patients, and this method can be safely used to supplement local anesthesia. Ketamine has been demonstrated in several studies to have both anesthetic and anti-inflammatory properties. In cases where ketamine is used together with local anesthetics in oral surgical procedures, it has proven to relieve postoperative pain16, 17, 18.

The best strategy and medicine to use on patients for predictable and effective pain management is still debatable, as the inflammatory reactions in patients after embedded third molar surgery depend on numerous factors19. There is a limited number of studies in the literature comparing the effectiveness of various medications on pain and trismus following third molar surgery. Furthermore, no study compares the efficacy of local submucosal ketamine with the preemptive analgesia method in third molar surgery. This randomized placebo-controlled clinical trial is the first to compare these two approaches in this manner. The study hypothesizes that these two drugs will be effective in managing pain and trismus in the postoperative period. The aim of the study was to compare the efficacy of preemptive ibuprofen, local ketamine, and their combinations in the treatment of postoperative pain and trismus following third molar surgery. The specific objective of the study is to determine the optimal method for managing pain and trismus after third molar surgery.