Nitrous oxide (N2O) has analgesic properties as determined in both animal and human research. In the present study, we sought to determine whether N2O 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 N2O 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 degrees 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 = "extremely" 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 N2O (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 N2O effects.(ABSTRACT TRUNCATED AT 250 WORDS)