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- 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; Cai, Yang; Kong, Hong; Pan, Yin-Bing; Jiang, Lai; Pan, Xiu-Xiu; Hu, Liang; Qian, Yan-Ning; Jiang, Chun-Yi; Liu, Wen-Tao
- Abstract
<bold>Background: </bold>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. <bold>Methods: </bold>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. <bold>Results: </bold>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. <bold>Conclusions: </bold>Procyanidins suppresses morphine-induced activation of NLRP3 inflammasome and inflammatory responses in microglia, and thus resulting in significant attenuation of morphine antinociceptive tolerance.
- Subjects
MORPHINE; PROCYANIDINS; INFLAMMASOMES; INTERLEUKIN-1 receptors; MICROGLIA; CELL metabolism; ANALGESICS; ANIMAL behavior; ANIMAL experimentation; BIOTRANSFORMATION (Metabolism); CELLS; COMPARATIVE studies; DRUG synergism; DRUG tolerance; INTERLEUKIN-1; RESEARCH methodology; MEDICAL cooperation; MICE; NARCOTICS; PROTEINS; RESEARCH; TRANSFERASES; DNA-binding proteins; EVALUATION research; PAIN measurement; PHARMACODYNAMICS
- Publication
Journal of Neuroinflammation, 2016, Vol 13, p1
- ISSN
1742-2094
- Publication type
journal article
- DOI
10.1186/s12974-016-0520-z