Modulatory role of estradiol in nicotinic antinociception in adult female rats.

Aims: Differences in the response to nicotinic analgesia in males and females have been suggested by recent studies, and such differences are presumed to be due to the regulatory effects of gonadal hormones. The aim of this study was to investigate nicotinic antinociception and the effect of estradiol (E2) on this response in female rats.

Main Methods: Ovariectomized female rats were implanted with subcutaneous silastic tubes containing E2. On day 28 after implantation, epibatidine, a high-potency nicotinic acetylcholine receptor (nAChR) agonist, was administered intrathecally, and antinociception at the spinal level was assessed by the tail-flick test. In addition, immunohistochemical staining for nAChRalpha4 was performed in spinal cord sections.

Key Findings: We found that female rats showed shorter nociceptive latencies than males, but there was no effect of ovarian status. However, OVX significantly increased epibatidine-induced antinociception compared to that in intact females, and this increase was attenuated by E2 treatment. In addition, OVX resulted in increased nAChRalpha4 immunostaining in the dorsal horn compared to that in intact females, and this increase was also attenuated by E2 treatment.

Significance: Results of this study provide new evidence that E2 modulates epibatidine-induced antinociception at the spinal level in female rats.