Nitrous oxide produces a biphasic effect on opiate-induced muscle rigidity in the rat

Muscle rigidity is a side effect of potent opiate agonists like alfentanil. Older clinical studies suggested that nitrous oxide (N2O) augments opiate rigidity, but this has never been rigorously examined in an animal model. Sixty-two Wistar rats were placed in a Plexiglas box through which fresh gas flowed at 4 l/min. Muscle rigidity was assessed using gastrocnemius electromyographic (EMG) activity. Rats were exposed to either 60% N2O in O2 or 100% O2, EMG was measured for 10 min, alfentanil (0, 50, 175, or 350 micrograms/kg) was administered intravenously, and data were collected for 45 min. Alfentanil produced a dose-dependent increase in EMG activity in both O2 and N2O groups (p < 0.001). At 1 min postalfentanil, N2O caused significantly more rigidity than 100% O2 (p < 0.001). However, beginning at 5 min, N2O attenuated both the magnitude and the duration of rigidity. Study of a separate group of animals breathing 30% O2 demonstrated that N2O's attenuating effect on alfentanil rigidity was not due to reduced inspired oxygen concentration. These results are described by a theoretical model of the pharmacodynamic interactions of alfentanil and nitrous oxide.