Pain and inflammation are predictable sequelae following tissue injury, such as surgery. Conventional treatment for intraoperative and postoperative control of pain includes local anesthetic administered preoperatively and analgesics administered postoperatively. Disadvantages of these approaches include pain during the interval when the effect of local anesthesia dissipates and the postoperatively administered analgesic takes effect and adverse effects of opioid-containing analgesics in ambulatory patients. Research over the past two decades has demonstrated that administering nonsteroidal anti-inflammatory drugs (NSAIDs) preoperatively significantly reduces the intensity and the duration of postoperative pain up to eight hours (Dionne et al., 1978 and Jackson et al., 1989). Parallel clinical investigations suggest that the pre-emptive treatment with a long-acting local anesthetic or an NMDA-antagonist reduces pain at 24 to 72 hours post-surgery (Gordon et al., 1997; Yamamoto et al., 1993; Gordon et al., 1999). This proposed clinical trial will use the oral surgery model to assess the therapeutic efficacy of pre-emptive and preventive treatment with a potent selective COX-2 inhibitor, rofecoxib (Vioxx® (Registered Trademark)), given prior to and following third molar extractions to reduce postoperative pain at 24 and 48 hours post-surgery.

This study is a double-blind, randomized control trial with parallel groups using placebo, ibuprofen, or rofecoxib. Rofecoxib 50 mg will be administered PO 90 minutes before surgery in the Clinical Center at NIH and another 50 mg will be self-administered 24 hours later by the subjects at their homes. This regimen is predicted to suppress the onset and intensity of post-operative dental pain to a greater extent than placebo or a non-selective COX-1/COX-2 inhibitor (ibuprofen). The analgesic effect of the drugs will be estimated by hourly observations over the first four hours after surgery using two different measures of pain intensity, the category scale and a visual analog scale (VAS). It is hypothesized that the pre-emptive administration of a selective COX-2 inhibitor, rofecoxib will inhibit the development of central and peripheral sensitization following tissue injury which manifests as hyperalgesia at later time points.

INCLUSION CRITERIA

Male or female volunteers referred for third molar extraction willing to undergo 3 visits: 1 screening visit, 1 surgical appointment, and 1 follow-up research-related appointment.

Between the ages of 16 to 35 years (based upon eruption patterns and age-related complications associated with surgical extraction of third molars)

In general good health- American Society of Anesthesiologists (ASA) status I or II (healthy subjects based upon criteria for safe administration of out-patient conscious sedation)

Willing to undergo observation period for four hours post-operatively

Willing to complete a 100 mm visual analog scale and a category scale every hour for the first 4 post-operative hours, and again at 24 and 48 hours

Willing to have a preoperative biopsy on the day of surgery and a postoperative biopsy at 48 hours

Willing to return 48 hours to return completed pain diaries and for the postoperative biopsy

Sum total of the assessment of surgical difficulty ratings (Screening visit) must be between 8 to 14 in order to evaluate subjects experiencing similar pain levels.

EXCLUSION CRITERIA

Allergy to aspirin or NSAIDS

Pregnant or lactating females

History of peptic ulcers and GI bleeding

Chronic use of medications confounding the assessment of the inflammatory response or analgesia ( antihistamines, NSAIDS, steroids, antidepressants, sulfa drugs)

Presence of a clinical signs suggestive of infection or inflammation

Unusual surgical difficulty

Surgical difficulty assessment rating less than 8 or greater than 14