Experimental study of metformin in relieving bone cancer pain by inhibiting JNK and improving gap junction function
10.11665/j.issn.1000-5048.20190310
- VernacularTitle:二甲双胍抑制JNK改善缝隙连接功能缓解骨癌痛的实验研究
- Author:
Yufeng GU
1
;
Xiuxiu PAN
;
Ling SONG
;
Xing YANG
;
Liang HU
;
Wentao LIU
Author Information
1. 南京医科大学江苏省神经退行性疾病重点实验室
- Publication Type:Journal Article
- Keywords:
metformin;
astrocytes;
bone cancer pain;
JNK;
gap junction
- From:
Journal of China Pharmaceutical University
2019;50(3):337-343
- CountryChina
- Language:Chinese
-
Abstract:
This study aims to explore the involvement of c-Jun N-terminal kinase(JNK)-Gap junction regulation in the rat model of bone cancer pain and figure out whether adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK )activator metformin could attenuate bone cancer pain through this mechanism. Tumor cell implantation(TCI)induced bone cancer pain model in rats was established. The rats were administered, respectively, with 20 μL of metformin(50, 100 μg), JNK inhibitor SP600125(10 μg), gap junction inhibitor(carbenoxolone, CBX)(10 μg)and AMPK inhibitor Compound C(CC)(10 μg). The Von Frey Assay was applied to test the mechanical pain threshold. The activity of Glial fibrillary acidic protein(GFAP), ionized calcium-binding adaptor molecule 1(IBA-1)and Connexin 43(Cx43)in spinal cord was evaluated by immunohistochemistry. Changes of p-JNK expression were detected by Western blot. JNK inhibitor SP600125 relieved TCI-induced bone cancer pain significantly in rats, while this analgesic effect was almost canceled by the blocker of gap junction carbenoxolone(CBX). Various concentration of metformin(50, 100 μg, i. t. )significantly inhibited TCI-induced mechanical allodynia and the changes of p-JNK and p-Cx43 expression were also reversed in spinal cord in rats. Together, these data suggested that activation of AMPK with metformin attenuated TCI-induced bone cancer pain via regulating the function of JNK-Gap junction in rats.
