Long-Term Influences of Neonatal Pain-Related Stress on Cognitive and Stress-Hormonal Functions in Rats: Age and Sex Aspects.

To address the problem of neonatal pain-related stress effects on spatial learning, memory and the stress reactivity of the hypothalamo–pituitary–adrenal axis (the HPA) in adolescent and adult rats we gave male and female rats an intraplantar injection of moderate concentration of formalin (2.5%, 0.5 µL) (Formalin rats) on postnatal days (P1 and P2). Adolescent male Formalin rats showed expressed impairments in both learning and memory. Adult male and female Formalin rats displayed better spatial learning than the adolescent Formalin rats; males, regardless of age, revealed better ability in learning than females. Adult Formalin males showed higher HPA axis reactivity, which was combined with a higher performance of long-term memory compared with the corresponding data in adult females. The data demonstrate that the consequences of moderate neonatal pain-related stress manifested themselves in later life differently depending on the age and sex. Moreover, the results testify to an unconventional adaptive potential of pain-related stress, which, when interacting with behavioral plasticity, improved the functioning of neurobiological systems in adult rats. The identified sex differences in effects of pain-related stress on the cognitive functions in rats of both ages, as well as the stress reactivity of hormonal response in adult rats, suggest sexual dimorphism in neonatal pain-triggered synaptic plasticity of structures involved in spatial learning and memory. [ABSTRACT FROM AUTHOR]