Interaction of lead acetate with calcium channel blockers in formalin test and formalin-induced inflammation

  In this study 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. In order to study nociception, formalin test was selected because of greater resemblance to clinical pain. Lead acetate (50, 75, l00, 125 and 150 mg/kg) administered intraperitoneally 90 minutes 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. Different doses of lead acetate induced a dose-dependent anti- nociception in both phases of formalin test. When animals were administered alone by calcium channel blockers, among them diltiazem and verapamil did not induce any significant effect in both phases of formalin test but nifedipine induced anti-inflammatory effect in late phase significantly (p<0.01). Pretreatment of animals with nifedipine and verapamil potentiated lead acetate anti-nociceptive effect (early phase) in doses of 50, 75 and 50 mg/kg, respectively. Both nifedipine and diltiazem augmented lead acetate anti-inflammatory effects (late phase) in all doses used. Pretreatment of animals with verapamil did not affect lead acetate anti-nociceptive or anti-inflammatory effects. Based on these data, tile association between calcium channel blockers and lead may be explained as a synergistic action rather than a simple dose combination of both agents. It is concluded that L-type calcium channels are susceptible to lead acetate that may be blocked during lead poisoning but different L-type calcium channel subtypes have different sensitivity to lead neurotoxicity.