Ovariectomy modulation of morphine analgesia of neuropathic pain is associated with the change of K(+)-Cl(-) cotransporter 2 protein level in spinal dorsal horn.

Sex differences in opioid analgesia have been confirmed both in clinical and experimental studies. Gonadal hormones (estrogens in particular) have a great role in this process. However, the mechanisms that underlie these sex differences are not very clear. In this study, we used K(+)-Cl(-) cotransporter 2 (KCC2) as a molecule target to investigate the mechanism underlying the phenomenon. Sprague-Dawley rats were randomly assigned to ovariectomy (OVX)+morphine group, OVX+Saline group, sham surgery (OVX-sham)+morphine group and OVX-sham+saline group. All the rats received SNI surgery three weeks after ovariectomy. We used von Frey values as a sign of neuropathic pain. On PO day 14, 1 μg morphine or the vehicle saline was administered intrathecally via a PE-10 catheter formerly implanted. Hindpaw withdrawal threshold was determined before and 30, 60, 90, 120, 150, 180 min after drugs injection. The L4-L5 segments of the spinal cord were removed and immunoblotted for KCC2 protein at the time of 2 and 3 h after drugs administration. We find that ovariectomy can regulate the sensitivity to morphine analgesia of neuropathic pain and KCC2 protein level will change in the spinal dorsal horn.