Effects of chronic stress on nitrous oxide (N2O)‐induced antinociceptive and anxiolytic effects in mice

Abstract

Subanesthetic concentrations of N2O are routinely used in clinical dentistry to produce conscious sedation. The aim of this study was to assess the influence of chronic stress on the antinociceptive and anxiolytic effects of N2O. To induce chronic stress, male NIH Swiss mice (20–25 g) were subjected to a modified forced‐swim test four times over 48 min. Thirty min later, they were exposed to 30%, 50% or 70% N2O in O2, and antinociceptive or anxiolytic responsiveness was assessed using the hot plate test or the light/dark exploration box. Non‐stressed control mice responded to N2O with a dose‐dependent antinociceptive effect, but chronically‐stressed, N2O‐exposed mice showed a marked hyperalgesic response. Exposure of non‐stressed control mice to N2O increased both the time spent in the light compartment and the number of intercompartmental transitions in a generally dose‐dependent manner. Chronic stress did not influence either parameter, but chronically‐stressed, N2O‐exposed mice showed increases in the number of transitions but not in time spent in the light compartment. These findings may be of clinical significance in the use of N2O in patients with chronic stress. Further investigation in the influence of stress on the antinociceptive and anxiolytic actions of N2O is warranted. (Supported in part by NIH Grant GM‐77153 and the Allen I. White Distinguished Professorship.)