Endogenous gonadal hormones regulate females' behavioral responses to formalin through prostaglandin E2 release.

Introduction: This study aimed to determine if endogenous gonadal hormones affect the intracellular mechanisms in the spinal cord that control inflammatory pain responses.

Methods: We analyzed behavioral responses to, and changes in, serum levels of prostaglandin E2, estradiol, progesterone, and corticosterone after administration of 5% formalin in intact and ovariectomized (OVX) female rats.

Results: OVX females displayed significantly more flinching than did intact females during Phase I, and after formalin administration their corticosterone levels were significantly lower. No differences were seen across COX-1 and COX-2 protein expression in the spinal cord of either naive or formalin-treated rats. However, subsequent to formalin a main effect of gonadectomy was seen in prostaglandin E2 levels; OVX animals had significantly lower prostaglandin E2 levels than intact animals.

Conclusions: These results indicate that in female rats nociceptive responses to formalin are regulated through the levels of prostaglandin E2, an important mediator in inflammation, whereas protein levels of COX-1 and COX-2 play a more limited role.