Title |
Procyanidins alleviates morphine tolerance by inhibiting activation of NLRP3 inflammasome in microglia
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Published in |
Journal of Neuroinflammation, March 2016
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DOI | 10.1186/s12974-016-0520-z |
Pubmed ID | |
Authors |
Yang Cai, Hong Kong, Yin-Bing Pan, Lai Jiang, Xiu-Xiu Pan, Liang Hu, Yan-Ning Qian, Chun-Yi Jiang, Wen-Tao Liu |
Abstract |
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. 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. 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. Procyanidins suppresses morphine-induced activation of NLRP3 inflammasome and inflammatory responses in microglia, and thus resulting in significant attenuation of morphine antinociceptive tolerance. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 63 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 10 | 16% |
Student > Master | 8 | 13% |
Researcher | 7 | 11% |
Student > Doctoral Student | 5 | 8% |
Student > Bachelor | 4 | 6% |
Other | 13 | 21% |
Unknown | 16 | 25% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 9 | 14% |
Neuroscience | 9 | 14% |
Agricultural and Biological Sciences | 7 | 11% |
Pharmacology, Toxicology and Pharmaceutical Science | 6 | 10% |
Immunology and Microbiology | 4 | 6% |
Other | 7 | 11% |
Unknown | 21 | 33% |