Sex difference in the brain response to formalin-induced nociceptive stimuli as revealed by the expression of phosphorylated cAMP response element binding protein (pCREB) as a marker of neuronal activation

It is widely accepted that there is a sex difference in nociceptive responses. For example, females are more sensitive to formalin-induced nociceptive stimuli than males. In the present study, we examined whether there was a sex difference in the brain responses to formalin-induced nociceptice stimuli or not, by checking the expression of pCREB in cells of the accumbens nucleus (ACB) and the bed nucleus of the stria terminalis (BST) including the lateral and medial subdivisions. Adult male and female Wistar rats were injected s.c. with saline or 2% formalin dissolved in 50 μl of saline into the planter surface of the right hindpaw. They were killed by an over dose of pentbarbital sodium 5 min after the injection and served to immunohistochemical processing. We found that the number of pCREB expressing cells in both sides of the ACB and BST in male rats injected with formalin was not different from that in male rats injected with saline. In contrast, the number of pCREB expressing cells in both sides of these areas of female rats injected with formalin was significantly greater than that of female rats injected with saline. In saline-injected rats, there was no significant sex difference in the number of pCREB expressing cells. These results show that more areas in the forebrain are activated by formalin injection in female rats than in male rats, suggesting a sex difference in the brain response to nociceptive stimuli. [Jpn J Physiol 54 Suppl:S173 (2004)]