MODULATION OF OPIOID ANTINOCICEPTION BY CCK AT THE SUPRASPINAL LEVEL - EVIDENCE OF REGULATORY MECHANISMS BETWEEN CCK AND ENKEPHALIN SYSTEMSIN THE CONTROL OF PAIN

1 Much evidence in the literature supports the idea that cholecystokin in (CCK) interacts with opioids in pain mechanisms. In this work, we h ave investigated the supraspinal interactions between enkephalins and CCK, using the hot plate test in mice. 2 Intracerebroventricular (i.c. v.) administration of BDNL (a mixed CCK(A)/CCK(B) agonist) induced dos e-dependent antinociceptive responses on both paw lick and jump respon ses. In contrast, using the same test, the i.c.v. injection of BC 264 (a selective CCK(B) agonist) induced a hyperalgesic effect, which was restricted to paw licking and occurred only at a high dose of 2.5 nmol . 3 In addition, i.c.v. administration of BDNL potentiated the antinoc iceptive effects of the mixed inhibitor of enkephalin degrading enzyme s, RB 101 and of the mu-agonist, DAMGO, while BC 264 reduced these eff ects. 4 Furthermore, at a dose where it interacts selectively with del ta-opioid receptors, the opioid agonist BUBU reversed the hyperalgesic responses of BC 264 (2.5 nmol) but was unable to modify the effects i nduced by BDNL. 5 Taken together, these results suggest the existence of regulatory mechanisms between CCK and enkephalin systems in the con trol of pain. These regulatory loops could enhance the antinociceptive effects of morphine allowing the opiate doses used to be reduced and thus, possibly, the side-effects to be minimized.