Experimental study of metformin in relieving bone cancer pain by inhibiting JNK and improving gap junction function

GU Yufeng; PAN Xiuxiu; SONG Ling; YANG Xing; HU Liang; LIU Wentao

doi:10.11665/j.issn.1000-5048.20190310

Journal of China Pharmaceutical University > 2019 > 50(3): 337-343. > DOI: 10.11665/j.issn.1000-5048.20190310

GU Yufeng, PAN Xiuxiu, SONG Ling, YANG Xing, HU Liang, LIU Wentao. Experimental study of metformin in relieving bone cancer pain by inhibiting JNK and improving gap junction function[J]. Journal of China Pharmaceutical University, 2019, 50(3): 337-343. DOI: 10.11665/j.issn.1000-5048.20190310

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Experimental study of metformin in relieving bone cancer pain by inhibiting JNK and improving gap junction function

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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.
- metformin,
- astrocytes,
- bone cancer pain,
- JNK,
- gap junction

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Experimental study of metformin in relieving bone cancer pain by inhibiting JNK and improving gap junction function

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