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

Weijun Shen; Liang Shen; Guoqiang Chen; Fen Wang; Cheng Li; Fuqing Lin; Xiaohu Yang; Shukun Fu

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

Int J Clin Exp Med. 2014 Oct 15;7(10):3467-72. eCollection 2014.

Authors

Weijun Shen¹, Liang Shen², Guoqiang Chen¹, Fen Wang¹, Cheng Li¹, Fuqing Lin¹, Xiaohu Yang¹, Shukun Fu¹

Affiliations

¹ Department of Anesthesiology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University Shanghai 200072, China.
² Department of Anesthesiology, Ruijin Hospital Luwan Branch, School of Medicine, Shanghai Jiaotong University Shanghai 200020, China.

PMID: 25419384
PMCID: PMC4238531

Abstract

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.

Keywords: KCC2; Ovariectomy; estrogen; hyperalgesia; morphine; neuropathic pain.