Sex differences in effects of prenatal stress on specific biphasic behavioral response in nociceptive formalin test in adult rats

Remote effects of stress (immobilization) in pregnant females at critical stages of fetal development on pain sensitivity to a long-term nociceptive stimulus (formalin test) were studied in their female and male off-spring at the age of 90 days. Prenatal stress produced changes of the standardized specific biphasic behavior response (BBR), whose intensity was evaluated by the number of flexion and shakings and by duration of licking of thee extremity injected with formalin. Apart from intensity of the BBR, duration of its both phases and of interphase interval was determined. It was found that the response intensity by the licking pattern increased significantly at the first response phase reflecting acute pain in males, whereas at the second phase reflecting tonic pain, both in females and males; duration of the phases and interphase interval increased statistically significantly only in females. Thus, in the prenatally stressed adult rats, an increase of pain sensitivity to a long-term nociceptive stimulus producing inflammation has been revealed by the BBR patterns organized at the supraspinal, but not at the spinal CNS level. Sex differences were found in the acute phase intensity and in duration both of acute and of tonic response phase. The data obtained indicate different effects of prenatal stress on the nociceptive systems involved in realization of the BBR in the formalin test in adult females and males and are an essential argument in favor of the concept of different characteristics of the acute and tonic pain.