The highly selective δ agonist BUBU induces an analgesic effect in normal and arthritic rat and this action is not affected by repeated administration of low doses of morphine

Abstract

The effect of various doses of the selective δ agonist BUBU (Tyr- d-Ser( O-t-butyl)-Gly-Phe-Leu-Thr( O-t-butyl) on the vocalization threshold to paw pressure were compared in normal and arthritic rats, a suitable clinical model of chronic pain. In both group of rats, the intravenous 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 antinociceptive 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 animal, whereas at 3 mg/kg BUBU was ineffective in normal rats. The analgesic effects of BUBU (9 mg/kg in normal and 3 mg/kg in arthritic rats) were completely prevented by the selective δ antagonist naltrindole (1 mg/kg i.v. a dose devoid of analgesic potency per se), while they were not affected by the selective μ antagonist naloxone (0.05 mg/kg i.v.). In addition, 3 mg/kg i.v. of BUBU remained effective in morphine tolerant arthritic rats. These results suggest that δ opioid receptor activation can modulate the transmission of cutaneous mechanical nociceptive information in rats, especially in inflammatory pain conditions.