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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2016

Open Access 01-12-2016 | Research

Procyanidins alleviates morphine tolerance by inhibiting activation of NLRP3 inflammasome in microglia

Authors: Yang Cai, Hong Kong, Yin-Bing Pan, Lai Jiang, Xiu-Xiu Pan, Liang Hu, Yan-Ning Qian, Chun-Yi Jiang, Wen-Tao Liu

Published in: Journal of Neuroinflammation | Issue 1/2016

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Abstract

Background

The development of antinociceptive tolerance following repetitive administration of opioid analgesics significantly hinders their clinical use. Evidence has accumulated indicating that microglia within the spinal cord plays a critical role in morphine tolerance. The inhibitor of microglia is effective to attenuate the tolerance; however, the mechanism is not fully understood. Our present study investigated the effects and possible mechanism of a natural product procyanidins in improving morphine tolerance via its specific inhibition on NOD-like receptor protein3 (NLRP3) inflammasome in microglia.

Methods

CD-1 mice were used for tail-flick test to evaluate the degree of pain. The microglial cell line BV-2 was used to investigate the effects and the mechanism of procyanidins. Reactive oxygen species (ROS) produced from BV-2 cells was evaluated by flow cytometry. Cell signaling was measured by western blot assay and immunofluorescence assay.

Results

Co-administration of procyanidins with morphine potentiated its antinociception effect and attenuated the development of acute and chronic morphine tolerance. Procyanidins also inhibited morphine-induced increase of interleukin-1β and activation of NOD-like receptor protein3 (NLRP3) inflammasome. Furthermore, procyanidins decreased the phosphorylation of p38 mitogen-activated protein kinase, inhibited the translocation of nuclear factor-κB (NF-κB), and suppressed the level of reactive oxygen species in microglia.

Conclusions

Procyanidins suppresses morphine-induced activation of NLRP3 inflammasome and inflammatory responses in microglia, and thus resulting in significant attenuation of morphine antinociceptive tolerance.
Appendix
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Metadata
Title
Procyanidins alleviates morphine tolerance by inhibiting activation of NLRP3 inflammasome in microglia
Authors
Yang Cai
Hong Kong
Yin-Bing Pan
Lai Jiang
Xiu-Xiu Pan
Liang Hu
Yan-Ning Qian
Chun-Yi Jiang
Wen-Tao Liu
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2016
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-016-0520-z

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