Role of L-type calcium channels in lead acetate-induced antinociceptive effects on formalin test in mice

In this study, the interaction of three types of calcium channel blockers-nifedipine, diltiazem, and verapamil-on the effects of lead acetate on two types of pain (nociception and inflammation) induced by formalin in mice were examined. To study nociception, the formalin test was selected because of greater resemblance to clinical pain. Lead acetate (50, 75, 100 125 150 mg/kg) was administered intraperitoneally 90 min before formalin injection. Nifedipine (5 mg/kg), diltiazem (10 mg/kg), and verapamil (5 mg/kg) alone or in combination with different doses of Lead acetate were used. Lead acetate induced a dose-dependent antinociception in both phases of the formalin test. When animals were administered calcium channel blockers alone, diltiazem and verapamil did not induce any significant effect in either phase of the formalin test, but nifedipine induced anti-inflammatory effects in the late phase (p <.01). Pretreatment with nifedipine or diltiazem potentiated the bead acetate antinociceptive effect (early phase) in doses of 50 and 75 mg/kg and 50 mg/kg, respectively. Both nifedipine and diltiazem augmented bead acetate anti-inflammatory effects (late phase) in all doses used. Pretreatment of animals with verapamil did not affect lead acetate antinociceptive or anti-inflammatory effects. Based on these data, the association between calcium channel blockers and lead acetate may be explained as a synergistic action rather than a simple dose combination of both agents. It is concluded that L-type calcium channels may be blocked during lead acetate poisoning, but different L-type calcium channel subtypes have different sensitivities to lead neurotoxicity.