Differences in adaptive behaviors of adolescent male and female rats exposed at birth to inflammatory pain or stress

In adolescent rats (25-35-day-old) exposed at birth (neonatal days 1 and, repeatedly, 2) to adverse impacts (inflammatory pain, short-term maternal separation stress, or both), sexual dimorphism was found in pain behavior under identical peripheral inflammation conditions. Our priority data indicate an enhancement of pain response in the formalin test in males, whereas in females pain sensitivity did not change, i.e. pain experienced in females at birth did not affect the system reactivity to the same chemical irritant in the adolescent period. However, rats of both sexes exposed to short-term maternal deprivation stress (60 min on neonatal days 1 and 2) exhibited the enhanced pain sensitivity in the formalin test. The combined impact of inflammatory pain and maternal deprivation in neonatal pups did not change pain sensitivity at adolescence both in males and females. Male and female rats exposed to early maternal deprivation exhibited decreased anxiety levels in the elevated plus-maze; rats exposed to each of the above-mentioned early impacts showed a decline in adaptive behavior in the forced swim test; males exposed to pain and combined impacts demonstrated the spatial learning impairment in the Morris labyrinth. Thus, we have pioneered in demonstrating sex-dependent differences in the effect of inflammatory pain in neonatal rat pups on the inflammatory pain sensitivity in adolescent rats. The division of early stress and pain impacts was revealed in adolescent females in the formalin test: while maternal deprivation induced hyperalgesia, pain did not change the tonic nociceptive system functional activity.