Sex differences in the effects of prenatal stress on stress-induced analgesia

Prenatal stress (PS) is known to cause demasculinizing and feminizing effects on sexually dimorphic behavior in laboratory animals. In three separate experiments performed on the same subjects at 10 week intervals, nociceptive sensitivity and the analgesic response to a cold-water swim stress were assessed in adult male and female Swiss-Webster mice that were either stressed prenatally or nonstressed (NS) control subjects. Experiment 1 showed analgesic magnitude to increase in female mice as a result of PS compared to nonstressed controls, whereas no changes were noted in male subjects. The increase in analgesia in female mice is maintained by estrogen. as gonadectomy eliminated the increase in Experiment 2, and estrogen replacement restored it in Experiment 3. Withdrawal latency to a noxious heat stimulus (hot-plate test) was also influenced by the PS manipulation; a decrease in hot-plate latency (indicating greater nociceptive sensitivity) was noted in PS subjects of both sexes in Experiment 1. Repeated testing (and/or age) may influence the effect of PS on nociceptive responses in a sex-dependent manner. The reduction in hot-plate latency was only present in males in Experiment 2, and was not present in either sex by Experiment 3. Thus, PS influences both baseline pain sensitivity and stress-induced analgesia responses in a sex and hormone-dependent fashion.