Acute Tolerance to Nitrous Oxide in Humans

Abstract

The goal of this research was to determine whether the level of analgesia produced by nitrous oxide remains constant for the duration of a typical dental procedure or whether acute tolerance reduces the drug's efficacy. A computer-controlled stimulator delivered brief (approx. 1 msec) electrical pulses to a vital maxillary incisor which had been found to have normal sensitivity in a preliminary session. Subjects were trained to indicate the occurrence of a barely perceptible sensation (i.e., detection threshold) as well as a minimally painful sensation (i.e., pain threshold). On the experimental day, all subjects breathed a non-odorized placebo gas mixture during a 10-min baseline condition, and were then randomly assigned to receive either an odorized placebo gas mixture or an odorized 35-40% nitrous oxide/oxygen gas mixture for 46 min. Detection and pain thresholds were assessed repeatedly during the baseline and gas exposure conditions. Placebo control subjects had little change of either sensory threshold. Subjects breathing nitrous oxide significantly increased both detection and pain thresholds within 2-8 min following the onset of the drug. However, maintenance of the drug's effect was not consistent between subjects, despite continuous administration of a constant concentration of nitrous oxide. Some subjects had a relatively constant elevation of sensory thresholds throughout the nitrous oxide administration period, and others returned to baseline sensitivity values and therefore were acutely tolerant.