<qa>  What is the effect of rofecoxib?All subjects N 136 will be healthy volunteers scheduled for third molar extractions. Using a double-blinded, randomized, parallel study design, subjects will be randomized into four groups. All patients will receive local anesthesia injections preoperatively either 2 lidocaine or 0.5 bupivacaine to manage surgical pain in conjunction with a preemptive medication either 50 mg of rofecoxib or placebo to control postoperative inflammation. The first dose of preemptive medication will be taken by mouth 90 minutes prior to conscious sedation and extractions, and later self-administered once a day for the next 48 hours. The analgesic effect of the drugs will be assessed in the clinic every 20 minutes for the first four hours after extractions, and then self-assessed at 24, and 48 hours after surgery using two pain intensity assessment instruments: category scale and visual analog scale VAS. Microdialysis will be performed with sample collection concurrent with pain report over the immediate postoperative period of four hours. Two biopsies will be performed: preoperatively, and postoperatively at 48 hours. The combination regimen with bupivacaine and rofecoxib is predicted to maximally suppress the onset and intensity of postoperative dental pain to a greater extent than all other groups through a blockade of the nociceptive input from both surgery and inflammation. It is hypothesized that this preemptive treatment will maximally inhibit the development of central sensitization following tissue injury which manifests as hyperalgesia at later time points. It is also hypothesized that the administration of rofecoxib a cyclooxygenase-2 selective anti-inflammatory medication will reduce post-surgical pain experienced at later time points to a greater extent than suppression of the intra-operative nociceptive barrage alone by bupivacaine, suggesting that suppression of inflammation plays a more pivotal role than attenuating nociception due to tissue injury in diminishing central sensitization. 