Potentiation of local lignocaine-induced sensory block by calcium channel blockers in rats

Abstract

We have studied the effects of three different types of calcium channel blockers (verapamil, diltiazem, and nicardipine) on local lignocaine sensory block. The standardized tail flick test was used to measure the duration and degree of lignocaine-induced conduction block in rats. After obtaining baseline tail flick latencies (mean 3.2 s), two 100-microliter doses of 0.3% lignocaine alone, a combination of verapamil 25, 100 or 200 micrograms, diltiazem 25, 100 or 200 micrograms, or nicardipine 0.5, 1.0 or 2.0 micrograms, and a large dose of calcium channel blockers (verapamil 200 micrograms, diltiazem 200 micrograms or nicardipine 2.0 micrograms) were injected on opposite sites of the tail base and the tail flick test was performed every 5 min for 45 min. A large dose of the calcium channel blockers showed no prolongation of tail flick latencies. Administration of 0.3% lignocaine alone produced a significant increase in tail flick thresholds and the peak effect of the percentage maximum possible effect (% MPE) was demonstrated at 5 min after drug injection (mean % MPE 28.8%; P < 0.01 vs baseline). Co-administration of 0.3% lignocaine and three doses of verapamil produced significant increases in area under the curve (AUC) in a dose-dependent fashion. Mean AUC values for 0.3% lignocaine alone and a combination of verapamil 25, 100 or 200 micrograms were 217.5, 502.5, 529.1 and 1600.3, respectively. Almost similar patterns of augmentation in AUC values were demonstrated after addition of different doses of diltiazem or nicardipine to 0.3% lignocaine. We conclude that the use of mixtures of local anaesthetic and calcium channel blocker potentiated lignocaine sensory block at the level of the peripheral nerves.