Capsaicin-evoked prostaglandin E2 release in spinal cord slices: relative effect of cyclooxygenase inhibitors.

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.