Ethanol augments pre-emptive analgesia produced by nitrous oxide in the formalin test in the rat

Experimental evidence suggests that the introduction of analgesia prior to a painful stimulus can reduce the subsequent pain (preemptive analgesia). Using the formalin test model, previous studies have demonstrated that general volatile anesthetics reduce the pre-emptive analgesia produced by nitrous oxide administration in the rat. The present study compared the influence of halothane and ethanol on the response to formalin injection in rats previously exposed or not exposed to nitrous oxide. Nitrous oxide decreased second phase licking behavior by approximately 70% from controls. Halothane decreased second phase licking by 37% from sham animals and, when administered with nitrous oxide, mitigated the suppression of licking seen with nitrous oxide alone. Ethanol reduced the licking response in both early and late phases following formalin injection. In contrast to halothane, ethanol failed to attenuate the analgesia produced by nitrous oxide administration alone. Thus, ethanol provides apparent analgesia following formalin injection and, unlike halothane, augments the preemptive analgesia produced by nitrous oxide.