Effects of subanesthetic concentrations of nitrous oxide on cold-pressor pain in humans

Abstract

Nitrous oxide (N 2O) has analgesic properties as determined in both animal and human research. In the present study, we sought to determine whether N 2O given in subanesthetic concentrations would reduce cold pressor (CP)-induced pain. A crossover, double-blind study was conducted in 10 healthy volunteers. Each subject participated in four separate sessions, and in each session the effects of one of four concentrations of N 2O in oxygen (0, 20, 30, and 40%) were assessed. The duration of inhalation was 40 min, and within each session, subjects immersed their nondominant arm in water (2–3 °C) twice for 3 min (at 10 and 30 min intrainhalation). Pain intensity, the degree to which the pain was bothersome (measured on a verbal scale of 0–10, 0 = “ not at all” and 10 = “ dextremely” painful/bothersome), and pain quality [measured by the short-form McGill Pain Questionnaire (SF-MPQ)] were assessed during the forearm immersion. Mood effects were measured with the use of visual analogue scales (VAS) in the presence and absence of pain. Self-reported pain intensity and bothersomeness, SF-MPQ ratings of “sharp pain” and “throbbing pain”, and VAS rating of “unpleasant bodily sensations” were significantly reduced by N 2O ( p < 0.05) in a concentration-dependent manner. Nitrous oxide had a number of effects on mood (e.g., increased VAS ratings of “stimulated”, “high”, “coasting”, “carefree”, and “having pleasant bodily sensations”). The cold-water immersion also influenced mood, but had little impact on modulating N 2O effects. Results from our study indicate that the CP test is a sensitive assay to measure the analgesic properties of subanesthetic concentrations of N 2O in humans.