CENTRAL ANTINOCICEPTIVE EFFECTS OF MELOXICAM ON RAT SPINAL-CORD IN-VITRO

NON-STEROIDAL anti-inflammatory drugs inhibit constitutive (COX-1) and induced cyclooxygenase (COX-2), blocking prostaglandin production. We have compared the effects on nociceptive reflexes of meloxicam, which is COX-2 selective, with indomethacin, which is non-selective, using an in vitro spinal cord preparation. Cords were taken from naive rats, and from rats with carrageenan-induced hyperalgesia of one hindpaw. R eflex thresholds were lower in carrageenan preparations. Superfusion w ith meloxicam (10-100 mu M) dose-dependently inhibited baseline reflex es and wind-up in normal and carrageenan preparations, whereas indomet hacin (100-300 mu M) had no effect. Thus meloxicam inhibits spinal ref lexes, whereas indomethacin does not, despite its high affinity for bo th COX isoforms. We conclude that meloxicam has spinal antinociceptive actions which cannot be explained by the current concept of COX inhib ition.