Cyclooxygenase (COX) plays an important role in the induction of pain and inflammation as well as the analgesic actions of NSAIDs and coxibs. This study evaluates the expression of the two isoforms COX-1 and COX-2 in a clinical model in which the surgical removal of impacted third molars is used to evaluate the analgesic activity of anti-inflammatory drugs. A 3-mm punch biopsy was performed on the oral mucosa overlying 1 impacted third molar immediately before extraction of 2 impacted lower third molars. After the second tooth was extracted, a second biopsy was performed adjacent to the surgical site either immediately after surgery or 30, 60, or 120 minutes after surgery. RNA was extracted from the biopsy specimens, and RT-PCR was performed to assess mRNA levels of COX-1, COX-2, and glyceraldehyde-3-phosphate dehydrogenase (G3PDH). The RT-PCR products in the biopsy specimens were normalized to G3PDH and compared with baseline. COX-2 mRNA was progressively increased at 30, 60, and 120 minutes after surgery (P<.05); COX-1 mRNA was transiently decreased at 60 minutes during the postsurgical period (P<.05). The results demonstrate peripheral elevation of COX-2 after tissue injury, which may contribute to increased prostaglandin E(2) at the site of injury, pain onset, and the analgesic activity of both nonselective NSAIDs and selective COX-2 inhibitors.This clinical study uses a physiologically relevant model to determine the time course of expression of COX-1 and COX-2 in acute inflammation of the human oral mucosa. This study furthers our understanding of the contribution of the COX isoforms to acute pain.