THE HIGHLY SELECTIVE DELTA-AGONIST BUBU INDUCES AN ANALGESIC EFFECT IN NORMAL AND ARTHRITIC RAT AND THIS ACTION IS NOT AFFECTED BY REPEATEDADMINISTRATION OF LOW-DOSES OF MORPHINE

The effect of various doses of the selective delta agonist BUBU (Tyr-D -Ser(O-t-butyl)-Gly-Phe-Leu-Thr(O-t-butyl) on the vocalization thresho ld to paw pressure were compared in normal and arthritic rats, a suita ble clinical model of chronic pain. In both group of rats, the intrave nous administration of BUBU (6, 9, 12 mg/kg in normal and 1.5, 3, 6 mg /kg in arthritic rats) led to significant antinociceptive effects. The same dose of BUBU (6 mg/kg i.v.) produced a much more potent antinoci ceptive effect in arthritic than in normal rats, and a dose as low as 1.5 mg/kg produced a significant analgesic effect in the arthritic ani mal, whereas at 3 mg/kg BUBU was ineffective in normal rats. The analg esic effects of BUBU (9 mg/kg in normal and 3 mg/kg in arthritic rats) were completely prevented by the selective delta antagonist naltrindo le (1 mg/kg i.v. a dose devoid of analgesic potency per se), while the y were not affected by the selective mu antagonist naloxone (0.05 mg/k g i.v.). In addition, 3 mg/kg i.v. of BUBU remained effective in morph ine tolerant arthritic rats. These results suggest that delta opioid r eceptor activation can modulate the transmission of cutaneous mechanic al nociceptive information in rats, especially in inflammatory pain co nditions.