Browsing School of Dentistry by Author "Khan, Asma A."
Cyclooxygenase expression and acute inflammatory pain in humansKhan, Asma A.; Capra, Norman F. (2002)Inhibition of cyclooxygenase (COX) activity is accepted to be the mechanism by which non-steroidal anti-inflammatory drugs (NSAIDs) exert their effects. Two distinct isoforms of COX have been identified: COX-1, which is constitutively expressed; and COX-2, which is primarily inducible by inflammation. It is hypothesized that the therapeutic effects of NSAIDs are attributable to inhibition of COX-2, while the adverse effects result from inhibition of COX-1. This led to the development of selective COX-2 inhibitors, a class of NSAIDs designed to selectively inhibit COX-2. This investigation characterized the expression of COX during acute inflammation and demonstrated the in vivo selectivity of celecoxib, a prototypic selective COX-2 inhibitor. The first study involved collection of biopsies from the oral mucosa of subjects immediately before extraction of their impacted lower third molars. A second biopsy was performed either immediately after surgery, 30, 60 or 120 minutes after surgery, or at pain onset. Messenger ribonucleic acid (mRNA) levels of COX-1 and COX-2 were assessed by RT-PCR. COX-1 mRNA was transiently decreased during the post-surgical period, while COX-2 expression was clearly induced after surgery. COX-2 protein was detected in the vascular endothelial cells, fibroblasts and polymorphonuclear cells in the biopsies.;In the second study, subjects received a dose of either celecoxib 200 mg (a selective COX-2 inhibitor), ibuprofen 600 mg, or placebo 8 hours before surgery and a second dose one hour before extraction of two lower impacted third molars. Microdialysis probes were placed for sample collection under the mucoperiosteal flap raised for surgery. Pain intensity ratings were collected every 20 minutes for 4 hours using a visual analog scale and a category scale. The samples were assayed by enzyme immunoassay for prostaglandin E2 (PGE2) an algesic and proinflammatory prostaglandin, and thromboxane B2 (TxB2). Both celecoxib and ibuprofen had a significant analgesic effect as compared to placebo. Celecoxib suppresses PGE2, a measure of both COX-1 and COX-2, and has no effect on TxB2, which is attributed to COX-1 activity. These data support celecoxib being a selective COX-2 inhibitor in vivo.