CAPSAICIN-EVOKED PROSTAGLANDIN E(2) RELEASE IN SPINAL-CORD SLICES - RELATIVE EFFECT OF CYCLOOXYGENASE INHIBITORS

The release of prostaglandin E(2) was examined from superfused spinal cord slices. The addition of capsaicin to the perfusate resulted in a dose-dependent increase of prostaglandin E(2)-like immunoreactivity. C apsaicin (10 mu M) evoked prostaglandin E(2) 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 mu M), 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 E(2), but resulted in a con centration-dependent suppression of capsaicin-evoked release of prosta glandin E(2). The IC50 values (in mu M) were: indomethacin: 0.7, S(+)- flurbiprofen: 2.0, acetaminophen: 4.4, ketorolac: 5.0, R(-)-flurbiprof en: 8.7, S(+)-ibuprofen: 9.5, and for R(-)-ibuprofen: > 10. The relati ve potency for the NSAIDs to reduce capsaicin-evoked prostaglandin E(2 ) release, with the exception of acetaminophen, corresponds to their a ntinociceptive activity after spinal delivery, a finding which further supports the role of prostanoids in spinal nociceptive processing.