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 μ, δ and κ 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 μ opioid receptor agonists, but not δ and κ 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 μ opioid receptors in the process of analgesia.