Effects of unpredictable chronic mild stress of female rats before pregnancy on morphine-induced antinociceptive tolerance in offspring.

Background: Prenatal chronic stress can impact pain sensitivity and analgesic responses in offspring. This study investigates oxidative stress markers in the ovaries of female rats that experienced unpredictable chronic mild stress (UCMS) before pregnancy and development of morphine analgesic tolerance in their offspring.

Methods: In this experimental study, 23 adolescent Wistar rats, 22 female and one male (6-8 weeks), were used as breeding pairs. The rats were maintained in a controlled environment with a 12-hour light/dark cycle and had unrestricted access to food and water. For one month prior to mating, the female rats were subjected to UCMS. After this exposure, the females were mated with a single male rat. Following lactation, male offspring received a daily dose of 10 mg/kg morphine intraperitoneally for 7 days, and the analgesic effects of morphine were assessed using the hot plate test. Ovarian tissues from the female rats exposed to UCMS were analyzed for oxidative stress markers.

Results: Pre-pregnancy UCMS significantly reduced morphine's antinociceptive potency, with the peak effect on day 1 being stronger in the stressed group (P < 0.0001). The cumulative antinociceptive effect over 7 days was significantly higher in the morphine-unstressed group (P < 0.01). UCMS increased malondialdehyde levels and decreased glutathione (P < 0.01), superoxide dismutase and catalase activities in maternal ovarian tissues (P < 0.05).

Conclusions: Maternal UCMS increased oxidative stress markers in the ovaries and might relate to altered morphine antinociceptive potency in offspring, suggesting epigenetic effects of parental stress on pain management in future generations.