The effects of a cold-water stimulus on butorphanol effects in males and females.

Using a crossover, randomized, double-blind, cumulative-dosing procedure, we examined whether a painful stimulus modulated subjective and psychomotor effects of butorphanol in eight male and eight female volunteers. During each session, volunteers received four intravenous injections of either butorphanol (0, 0.5, 1, and 2 mg/70 kg) or saline (placebo) at hourly intervals. Saline and butorphanol were tested in two conditions, forearm immersion 30 min after each injection into either 2 or 37 degrees C water. During the 180-s immersion, volunteers completed a visual analog scale (VAS), psychomotor test, and pain ratings. VAS ratings of "Coasting ('spaced out')", "heavy or sluggish feeling," and "sleepy" were lower in the 2 degrees C than in the 37 degrees C condition during butorphanol administration, but only in females. Modulation by a painful stimulus of sleepy ratings was confined to the third immersion (i.e., a dose effect). The cold-water stimulus significantly decreased butorphanol-induced impairment during the third immersion for males, and females showed a similar trend. Overall, pain ratings were higher in females, and although not significant, males reported a greater degree of analgesia. The differences in pain ratings and degree of analgesia between the sexes are discussed as a possible mechanism for the sex differences in modulatory effects.