THE EFFECTS OF OPIOID AND ALPHA(2) ADRENERGIC-BLOCKADE ON NONSTEROIDAL ANTIINFLAMMATORY DRUG ANALGESIA IN SHEEP

The analgesic effects of the non-steroidal anti-inflammatory drugs (NS AIDs) flunixin and dipyrone were assessed in healthy sheep with no pre -existing inflammation, and in sheep with a chronic inflammatory lesio n, using a mechanical noxious stimulus. Saline and dexamethasone were given as controls. Blood taken from healthy sheep after NSAID administ ration was assayed for thromboxane B-2 (TxB(2)) to compare the ability of these drugs to inhibit cyclo-oxygenase. Both flunixin and dipyrone produced a small but statistically significant rise in pain threshold s (18% and 21% of maximum possible effect respectively) in the healthy sheep which peaked at 30 min and had returned to pre-drug values by 2 -3 h. In the lame sheep a similar effect occurred but the response was smaller, much more variable and tended to be prolonged. Saline and de xamethasone had no effect on thresholds over 6 h in either group of sh eep. The rise in thresholds was prevented by pre-treatment with naloxo ne (an opioid antagonist) or atipamezole (an alpha(2)-adrenergic antag onist) in the healthy sheep. Naloxone and atipamezole had no effect on thresholds when given alone to healthy sheep. Both NSAIDs inhibited t he production of TxB(2) to a similar extent. These results indicate th at central mechanisms may be involved in NSAID analgesia.