Sex-related differences in the effects of morphine and stress on visceral pain.

The effect of morphine (in the absence of stress and after a type of naloxone-sensitive swim-stress) on the painful contractions induced by intraperitoneal injection of hypertonic saline was studied in four groups of rats: normally cycling females in oestrus, males, ovariectomized females and females subjected to constant light, to induce a hyperoestrogenemic state. In the absence of swim-stress, the sensitivity to morphine was maximum for males (i.e. analgesia was produced with the smallest doses). After swim-stress, both males and ovariectomized rats showed less sensitivity to the analgesic effect of morphine than normal females in oestrus, while females subjected to constant light were less sensitive. In females in natural oestrus, but not in the other groups, small doses (0.05 mg/kg) of morphine, paradoxically reduced the analgesic effect of swim-stress considerably. These results show the importance of sex-related factors in the sensitivity of visceral pain to morphine and stress. A selective role for endogenous androgens and oestrogens is likely.