Dexamethasone suppresses peripheral prostanoid levels without analgesia in a clinical model of acute inflammation.
OBJECTIVE
The therapeutic effects of glucocorticoids are generally attributed to suppression of multiple signaling pathways involved in the inflammatory response leading to decreased levels of inflammatory mediators at the site of injury. This study evaluated the in vivo relationship between levels of prostanoids at the site of tissue injury and analgesia after dexamethasone administration in a clinical model of tissue injury.


METHODS
Subjects were administered dexamethasone 4 mg or placebo 12 hours and 1 hour before the removal of 2 mandibular third molars. A microdialysis probe was implanted at each surgical site for measurement of immunoreactive prostaglandin E2 (PGE(2)) or immunoreactive thromboxane B(2) (TxB(2)), and pain was measured concurrently. Subjects received either ketorolac 30 mg intravenously or placebo at pain onset.


RESULTS
PGE(2) was detectable in the first postoperative sample, decreased over the next hour and then increased coincident with the onset of postoperative pain. Administration of dexamethasone suppressed PGE(2) levels in samples collected at pain onset in comparison to placebo and significantly suppressed TxB(2) at the surgical site but without any effect on pain report. Subsequent administration of ketorolac significantly reduced pain while decreasing both PGE(2) and TxB(2) levels at the surgical site.


CONCLUSIONS
The lack of an analgesic effect for dexamethasone while reducing both PGE(2) and TxB(2) at the site of injury in comparison to ketorolac analgesia accompanied by greater reductions in levels of these prostanoids suggests that glucocorticoids at this dose do not suppress PGE(2) release sufficiently to attenuate peripheral sensitization of nociceptors after tissue injury.
Dionne
Raymond A
RA
Pain and Naurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research/NIH, 10 Center Drive, Bethesda, MD 20892-2292, USA. rdionne@dir.nidcr.noh.gov
Gordon
Sharon M
SM
Rowan
Janet
J
Kent
Allison
A
Brahim
Jaime S
JS
D000328:Adult; D000698:Analgesia; D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D003907:Dexamethasone / Q000008:administration & dosage*; D015232:Dinoprostone / Q000037:antagonists & inhibitors*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D020910:Ketorolac / Q000008:administration & dosage*; D008297:Male; D008334:Mandible; D008964:Molar, Third / Q000601:surgery*; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*; D011182:Postoperative Care; D011300:Preoperative Care; D011446:Prospective Studies; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors*; D014081:Tooth Extraction; D014095:Tooth, Impacted / Q000601:surgery
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013929:Thromboxane B2; D003907:Dexamethasone; D015232:Dinoprostone; D020910:Ketorolac