Analgesic Effects of Morphine in Healthy Male and Female Volunteers. Sarton et al. (page 1245)

In most studies comparing analgesic effects of opioids in men and women, gender comparisons are not the primary focus of investigation. Accordingly, Sarton et al. designed a prospective study to compare analgesic effects of a bolus and a short infusion of morphine in healthy male (n = 10) and female (n = 10) volunteers. Pain was induced by an electrical current via  two electrodes placed on the skin overlaying the tibia of the left leg. The intensity of the noxious stimulus (pulses of 0.2 μs at 2 Hz) was increasedin steps of 10 mA, from the lowest of 10 mA to the maximum of 80 mA, at 6-s intervals. Participants were instructed to state “pain” when the stimulus became painful (pain threshold) and “stop” when the pain became intolerable (pain tolerance). This sequence of increasing stimulus intensity was performed twice at fixed intervals before, during, and after morphine administration. Men were tested by a male researcher, and women were tested by a female researcher.

The researchers observed that baseline pain threshold and pain tolerance currents were similar in both sexes. With intravenous administration, morphine had a greater potency in the women, as well as a slower onset and offset. The causes for sex differences in effect-site morphine concentrations (ke0) in the plasma samples obtained in this study were not clear, although the value of ke0observed in women parallels the ke0estimate for morphine-induced pupil constriction. These data agree with observed gender differences in morphine-induced respiratory depression and may explain higher postoperative opioid consumption in men compared with women.