Potentiation of morphine and clomipramine analgesia by cholecystokinin-B antagonist Cl-988 in diabetic rats

The aim of this study was to determine the influence of an intrathecally in jected cholecystokinin-B (CCK-B) receptor antagonist, Cl-988, on the analge sic effect of morphine and clomipramine in diabetic rats. Administered alon e, morphine (0.1 mg/kg, i.v.) and clomipramine (3 mg/kg, i.v.) have respect ively no effect and only a slight effect on vocalization thresholds to paw pressure in diabetic rats, but, when coadministered with Cl-988 (0.1 mu g/r at, i.t.), an appreciable antinociceptive effect was observed. This suggest s that a spinal blockade of cholecystokininergic system increases the analg esia induced by morphine or clomipramine. A CCK-B receptor antagonist could thus be used to lower dosages of morphine or antidepressant drugs in the m anagement of neuropathic pain in humans, and thereby reduce their side effe cts. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.