κ-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 κ-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 μg/kg, i.p.), the ED₅₀ 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 μg/h, 7 days) and sufentanil (2 μg/h, 8 days), the analgesic effect of U-69,593 was potentiated by 5-fold. Our results suggest a functional coupling between κ-opioid receptors and L-type Ca²⁺ channels in nociception.