title: Capsaicin-evoked prostaglandin E2 release in spinal cord slices: relative effect of cyclooxygenase inhibitors.
abstract: The release of prostaglandin E2 was examined from superfused spinal cord slices. The addition of capsaicin to the perfusate resulted in a dose-dependent increase of prostaglandin E2-like immunoreactivity. Capsaicin (10 microM) evoked prostaglandin E2 release from basal levels of 5.3 +/- 0.8 to 30 +/- 3 fmol/10 min fraction. The capsaicin-evoked release was blocked by the capsaicin receptor antagonist capsazepine (10 microM), but not by removal of extracellular Ca2+ ions. Addition of non-steroidal anti-inflammatory drugs (NSAIDs) to the perfusate had no effect on resting levels of prostaglandin E2, but resulted in a concentration-dependent suppression of capsaicin-evoked release of prostaglandin E2. The IC50 values (in microM) were: indomethacin: 0.7, S(+)-flurbiprofen: 2.0, acetaminophen: 4.4,ketorolac: 5.0, R(-)-flurbiprofen: 8.7, S(+)-ibuprofen: 9.5, and for R(-)-ibuprofen: > 10. The relative potency for the NSAIDs to reduce capsaicin-evoked prostaglandin E2 release, with the exception of acetaminophen, corresponds to their antinociceptive activity after spinal delivery, a finding which further supports the role of prostanoids in spinal nociceptive processing.
authors.affiliation: Department of Anesthesiology, University of California, San Diego, La Jolla, 92093.
authors.forename: A B
authors.initials: AB
authors.lastname: Malmberg
authors.forename: T L
authors.initials: TL
authors.lastname: Yaksh
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D011506:Proteins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D011506:Proteins; D015232:Dinoprostone; D002211:Capsaicin; D002118:Calcium