The role of spinal GABAB receptors in cancer-induced bone pain in rats

Zhou, Ya-Qun, Chen, Shu-Ping, Liu, Dai-Qiang, Manyande, Anne, Zhang, Wen, Yang, Shao-Bing, Xiong, Bing-Rui, Fu, Qiao-Chu, Song, Zhenpeng, Rittner, Heike, Ye, Da-Wei and Tian, Yu-Ke (2017) The role of spinal GABAB receptors in cancer-induced bone pain in rats. Journal of Pain, 18 (8). pp. 933-946. ISSN 1526-5900

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Abstract

Cancer-induced bone pain (CIBP) remains a major challenge in advanced cancer patients due to our lack of understanding of its mechanisms. Previous studies have demonstrated the vital role of GABAB receptors (GABABRs) in regulating nociception and various neuropathic pain models have shown diminished activity of GABABRs. However, the role of spinal GABABRs in CIBP remains largely unknown. In this study, we investigated the specific cellular mechanisms of GABABRs in the development and maintenance of CIBP in rats. Our behavioral results show that both acute and chronic intrathecal treatment with baclofen, a GABABR agonist, significantly attenuated CIBP-induced mechanical allodynia and ambulatory pain. The expression levels of GABABRs were significantly decreased in a time-dependent manner and colocalized mostly with neuron and a minority with astrocyte and microglia. Chronic treatment with baclofen restored the expression of GABABRs and markedly inhibited the activation of cAMP-dependent protein kinase (PKA) and the cAMP-response element-binding protein (CREB) signaling pathway.

Item Type: Article
Additional Information: © 2017 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Uncontrolled Keywords: Cancer-induced bone pain; GABAB receptor; PKA; CREB; Baclofen
Subjects: Medicine and health > Clinical medicine
Depositing User: Anne Manyande
Date Deposited: 21 Mar 2017 14:55
Last Modified: 31 Jul 2017 09:28
URI: http://repository.uwl.ac.uk/id/eprint/3242

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