Tolerance-like phenomenon of nifedipine-induced antinociception

We confirmed that repeated injection of nifedipine evokes an acute tolerance in rats. Nociceptive response was assessed by the tail-flick test. Rats, randomly divided into 3 groups, were injected once a week for 1 month with nifedipine intraperitoneally at the doses of: (A) 2 mg/kg; (B) 10 mg/kg; and (C) 10 mg/kg at the first injection and followed by dimethyl sulfoxide in the subsequent injections. After one month, group A and C were injected with 10 mg/kg and group B with 30 mg/kg nifedipine. In group A, 2 mg/kg of nifedipine did not change the TF latency but its repeated injections prevented the antinociceptive effect of 10 mg/kg nifedipine. In group B, only the first dose of 10 mg/kg and the last dose of 30 mg/kg produced a significant antinociception. In group C, the first but not the last dose of 10 mg/kg nifedipine, produced a significant antinociception. Our data suggest that a single dose of 10 mg/kg nifedipine or repeated doses of 2 mg/kg produced a tolerance-like phenomenon in nifedipine-induced antinociception.