Procyanidins alleviates morphine tolerance by inhibiting activation of NLRP3 inflammasome in microglia.
In: Journal of Neuroinflammation, Jg. 13 (2016-03-01), S. 1-14
Online
academicJournal
Zugriff:
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. [ABSTRACT FROM AUTHOR]
Titel: |
Procyanidins alleviates morphine tolerance by inhibiting activation of NLRP3 inflammasome in microglia.
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Autor/in / Beteiligte Person: | Cai, Yang ; Kong, Hong ; Pan, Yin-Bing ; Jiang, Lai ; Pan, Xiu-Xiu ; Hu, Liang ; Qian, Yan-Ning ; Jiang, Chun-Yi ; Liu, Wen-Tao |
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Zeitschrift: | Journal of Neuroinflammation, Jg. 13 (2016-03-01), S. 1-14 |
Veröffentlichung: | 2016 |
Medientyp: | academicJournal |
ISSN: | 1742-2094 (print) |
DOI: | 10.1186/s12974-016-0520-z |
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