L-type and T-type calcium channel blockade potentiate the analgesic effects of morphine and selective μ opioid agonist, but not to selective δ and κ agonist at the level of the spinal cord in mice

Abstract

We examined the effects of amlodipine, a selective L-type voltage dependent Ca(2+) channel (VDCC) blocker, and mibefradil, a selective T-type VDCC blocker on the antinociceptive effects of morphine, and mu, delta and kappa opioid receptor selective agonist-induced antinociception at the spinal level. Intrathecally administered amlodipine and mibefradil potentiated morphine and [D-Ala(2), N mePhe(4), Gly-ol(5)] enkephalin (DAMGO)-induced antinociception by shifting their dose response curves to the left. However, intrathecally administered amlodipine and mibefradil did not affect [D-Pen(2), D-Pen(5)]enkephalin (DPDPE) and [trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrolidinyl)cyclohexyl] benzene acetamide (U-50, 488H)-induced antinociception. These data indicate that L-type and T-type VDCC blockers synergistically potentiate the analgesic effects of mu opioid receptor agonists, but not delta and kappa opioid receptor agonists, at the spinal level. Additionally, these data suggest that there is an important functional interaction between L-type and/ or T-type VDCC and mu opioid receptors in the process of analgesia.