KAPPA-OPIOID RECEPTOR-MEDIATED ANTINOCICEPTION IN RATS IS DEPENDENT ON THE FUNCTIONAL-STATE OF DIHYDROPYRIDINE-SENSITIVE CALCIUM CHANNELS

The modulatory effect of the dihydropyridine Ca2+ channel antagonist nimodipine on the analgesic action of the kappa-opioid receptor agonist U-69,593 was analyzed using the tail-flick test in rats. The antinociceptive effect of U-69,593 (0.25-4 mg/kg) was antagonized by L-type Ca2+ channel blockade with nimodipine (200 mu g/kg, i.p.), the ED(50) being increased from 1.4 to 7.3 mg/kg. On the contrary, when an increase in the density of these channels was induced by means of chronic and simultaneous treatment with nimodipine (1 mu g/h, 7 days) and sufentanil (2 mu g/h, 8 days), the analgesic effect of U-69,593 was potentiated by 5-fold. Our results suggest a functional coupling between kappa-opioid receptors and L-type Ca2+ channels in nociception.