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Inhibition of Histone Deacetylases Attenuates Morphine Tolerance and Restores MOR Expression in the DRG of BCP Rats

The easily developed morphine tolerance in bone cancer pain (BCP) significantly hindered its clinical use. Increasing evidence suggests that histone deacetylases (HDACs) regulate analgesic tolerance subsequent to continuous opioid exposure. However, whether HDACs contribute to morphine tolerance in...

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Autores principales: He, Xiao-Tao, Zhou, Kai-Xiang, Zhao, Wen-Jun, Zhang, Chen, Deng, Jian-Ping, Chen, Fa-Ming, Gu, Ze-Xu, Li, Yun-Qing, Dong, Yu-Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962808/
https://www.ncbi.nlm.nih.gov/pubmed/29867508
http://dx.doi.org/10.3389/fphar.2018.00509
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author He, Xiao-Tao
Zhou, Kai-Xiang
Zhao, Wen-Jun
Zhang, Chen
Deng, Jian-Ping
Chen, Fa-Ming
Gu, Ze-Xu
Li, Yun-Qing
Dong, Yu-Lin
author_facet He, Xiao-Tao
Zhou, Kai-Xiang
Zhao, Wen-Jun
Zhang, Chen
Deng, Jian-Ping
Chen, Fa-Ming
Gu, Ze-Xu
Li, Yun-Qing
Dong, Yu-Lin
author_sort He, Xiao-Tao
collection PubMed
description The easily developed morphine tolerance in bone cancer pain (BCP) significantly hindered its clinical use. Increasing evidence suggests that histone deacetylases (HDACs) regulate analgesic tolerance subsequent to continuous opioid exposure. However, whether HDACs contribute to morphine tolerance in the pathogenesis of BCP is still unknown. In the current study, we explored the possible engagement of HDACs in morphine tolerance during the pathogenesis of BCP. After intra-tibia tumor cell inoculation (TCI), we found that the increased expression of HDACs was negatively correlated with the decreased expression of MOR in the DRG following TCI. The paw withdrawal threshold (PWT) and percentage maximum possible effects (MPEs) decreased rapidly in TCI rats when morphine was used alone. In contrast, the concomitant use of SAHA and morphine significantly elevated the PWT and MPEs of TCI rats compared to morphine alone. Additionally, we found that SAHA administration significantly elevated MOR expression in the DRG of TCI rats with or without morphine treatment. Moreover, the TCI-induced increase in the co-expression of MOR and HDAC1 in neurons was significantly decreased after SAHA administration. These results suggest that HDACs are correlated with the downregulation of MOR in the DRG during the pathogenesis of BCP. Inhibition of HDACs using SAHA can be used to attenuate morphine tolerance in BCP.
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spelling pubmed-59628082018-06-04 Inhibition of Histone Deacetylases Attenuates Morphine Tolerance and Restores MOR Expression in the DRG of BCP Rats He, Xiao-Tao Zhou, Kai-Xiang Zhao, Wen-Jun Zhang, Chen Deng, Jian-Ping Chen, Fa-Ming Gu, Ze-Xu Li, Yun-Qing Dong, Yu-Lin Front Pharmacol Pharmacology The easily developed morphine tolerance in bone cancer pain (BCP) significantly hindered its clinical use. Increasing evidence suggests that histone deacetylases (HDACs) regulate analgesic tolerance subsequent to continuous opioid exposure. However, whether HDACs contribute to morphine tolerance in the pathogenesis of BCP is still unknown. In the current study, we explored the possible engagement of HDACs in morphine tolerance during the pathogenesis of BCP. After intra-tibia tumor cell inoculation (TCI), we found that the increased expression of HDACs was negatively correlated with the decreased expression of MOR in the DRG following TCI. The paw withdrawal threshold (PWT) and percentage maximum possible effects (MPEs) decreased rapidly in TCI rats when morphine was used alone. In contrast, the concomitant use of SAHA and morphine significantly elevated the PWT and MPEs of TCI rats compared to morphine alone. Additionally, we found that SAHA administration significantly elevated MOR expression in the DRG of TCI rats with or without morphine treatment. Moreover, the TCI-induced increase in the co-expression of MOR and HDAC1 in neurons was significantly decreased after SAHA administration. These results suggest that HDACs are correlated with the downregulation of MOR in the DRG during the pathogenesis of BCP. Inhibition of HDACs using SAHA can be used to attenuate morphine tolerance in BCP. Frontiers Media S.A. 2018-05-15 /pmc/articles/PMC5962808/ /pubmed/29867508 http://dx.doi.org/10.3389/fphar.2018.00509 Text en Copyright © 2018 He, Zhou, Zhao, Zhang, Deng, Chen, Gu, Li and Dong. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
He, Xiao-Tao
Zhou, Kai-Xiang
Zhao, Wen-Jun
Zhang, Chen
Deng, Jian-Ping
Chen, Fa-Ming
Gu, Ze-Xu
Li, Yun-Qing
Dong, Yu-Lin
Inhibition of Histone Deacetylases Attenuates Morphine Tolerance and Restores MOR Expression in the DRG of BCP Rats
title Inhibition of Histone Deacetylases Attenuates Morphine Tolerance and Restores MOR Expression in the DRG of BCP Rats
title_full Inhibition of Histone Deacetylases Attenuates Morphine Tolerance and Restores MOR Expression in the DRG of BCP Rats
title_fullStr Inhibition of Histone Deacetylases Attenuates Morphine Tolerance and Restores MOR Expression in the DRG of BCP Rats
title_full_unstemmed Inhibition of Histone Deacetylases Attenuates Morphine Tolerance and Restores MOR Expression in the DRG of BCP Rats
title_short Inhibition of Histone Deacetylases Attenuates Morphine Tolerance and Restores MOR Expression in the DRG of BCP Rats
title_sort inhibition of histone deacetylases attenuates morphine tolerance and restores mor expression in the drg of bcp rats
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962808/
https://www.ncbi.nlm.nih.gov/pubmed/29867508
http://dx.doi.org/10.3389/fphar.2018.00509
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