The general anesthesia induced by various drugs differentially affects analgesia and its variability

Responses to noxious stimuli in awake animals are not totally consensual but are influenced by environmental factors. We considered the possibility that the influence of the environment could be reduced by induction of general anesthesia. We, therefore, compared responses to nociceptive thermal stimuli by measuring tail flick latency, a spinal reflex, in anesthetized and awake mice. All anesthetics tested decreased the intraindividual variability in the measurement of response, suggesting that environmental factors may account for much of this variability in the awake mouse. Mice treated with pentobarbital showed a graded response to increasing levels of heat but were unresponsive to either morphine or naloxone. In mice anesthetized with pentobarbital, increases in latencies occured only at very deep levels of anesthesia, while urethane increased and ketamine decreased latencies. The antinociceptive effect of urethane was unaffected by naloxone, but the nociceptive effect of ketamine was reversed by morphine. Thus, the various anesthetics could show differential effects towards opiate action. The decrease in statistical variability, the differential effects of general anesthetics on tail flick latency, and the distinctive effects of the different anesthetics on opiate action suggest that the anesthetized animal may be a useful tool in the study of nociception.