Effects of gestational stress and neonatal handling on pain, analgesia, and stress behavior of adult mice

Stressors presented during the late prenatal and early postnatal periods can have long-term effects on offspring behavior, due to the sensitive periods in the formation of brain circuitry associated with early development. This study investigated the long-term effects of prenatal (restraint during the last week of gestation) and postnatal (daily handling for 14 days postnatal) stress, alone and in combination, on adulthood pain behavior, analgesic responses to stress and morphine, and on behavioral indices of stress reactivity. We found that all of the adult responses measured were altered by perinatal manipulations. Nociceptive thresholds were increased by prenatal or by postnatal stress in males and females; application of both stressors in combination negated these effects. Elevations in morphine analgesia were also observed in animals undergoing either perinatal stressor, but not in those who received both stressors. Behavioral and analgesic responses to stress were consistent with previous observations of reduced stress responsiveness following neonatal handling, with some sex-specific findings. Male and female handled subjects exhibited decreases in stress behavior, and both groups of female handled subjects (regardless of prenatal stress [PS] condition) exhibited decreases in stress-induced analgesia (SIA). Males, on the other hand, exhibited decreases in SIA only if they were prenatally stressed (regardless of handling condition). Thus, prenatal and postnatal stressors have differing effects on the neural circuitry underlying pain, pain inhibition, and stress behavior. (C) 2003 Elsevier Science Inc. All rights reserved.