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Metformin reduces morphine tolerance by inhibiting microglial-mediated neuroinflammation

Overview of attention for article published in Journal of Neuroinflammation, November 2016
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (73rd percentile)

Mentioned by

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9 tweeters

Citations

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50 Dimensions

Readers on

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57 Mendeley
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Title
Metformin reduces morphine tolerance by inhibiting microglial-mediated neuroinflammation
Published in
Journal of Neuroinflammation, November 2016
DOI 10.1186/s12974-016-0754-9
Pubmed ID
Authors

Yinbing Pan, Xiaodi Sun, Lai Jiang, Liang Hu, Hong Kong, Yuan Han, Cheng Qian, Chao Song, Yanning Qian, Wentao Liu

Abstract

Tolerance seriously impedes the application of morphine in clinical medicine. Thus, it is necessary to investigate the exact mechanisms and efficient treatment. Microglial activation and neuroinflammation in the spinal cord are thought to play pivotal roles on the genesis and maintaining of morphine tolerance. Activation of adenosine monophosphate-activated kinase (AMPK) has been associated with the inhibition of inflammatory nociception. Metformin, a biguanide class of antidiabetic drugs and activator of AMPK, has a potential anti-inflammatory effect. The present study evaluated the effects and potential mechanisms of metformin in inhibiting microglial activation and alleviating the antinociceptive tolerance of morphine. The microglial cell line BV-2 cells and mouse brain-derived endothelial cell line bEnd3 cells were used. Cytokine expression was measured using quantitative polymerase chain reaction. Cell signaling was assayed by western blot and immunohistochemistry. The antinociception and morphine tolerance were assessed in CD-1 mice using tail-flick tests. We found that morphine-activated BV-2 cells, including the upregulation of p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation, pro-inflammatory cytokines, and Toll-like receptor-4 (TLR-4) mRNA expression, which was inhibited by metformin. Metformin suppressed morphine-induced BV-2 cells activation through increasing AMPK phosphorylation, which was reversed by the AMPK inhibitor compound C. Additionally, in BV-2 cells, morphine did not affect the cell viability and the mRNA expression of anti-inflammatory cytokines. In bEnd3 cells, morphine did not affect the mRNA expression of interleukin-1β (IL-1β), but increased IL-6 and tumor necrosis factor-α (TNF-α) mRNA expression; the effect was inhibited by metformin. Morphine also did not affect the mRNA expression of TLR-4 and chemokine ligand 2 (CCL2). Furthermore, systemic administration of metformin significantly blocked morphine-induced microglial activation in the spinal cord and then attenuated the development of chronic morphine tolerance in mice. Metformin significantly attenuated morphine antinociceptive tolerance by suppressing morphine-induced microglial activation through increasing AMPK phosphorylation.

Twitter Demographics

The data shown below were collected from the profiles of 9 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 57 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 57 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 16%
Researcher 9 16%
Student > Bachelor 7 12%
Student > Master 6 11%
Student > Doctoral Student 4 7%
Other 9 16%
Unknown 13 23%
Readers by discipline Count As %
Neuroscience 13 23%
Biochemistry, Genetics and Molecular Biology 7 12%
Pharmacology, Toxicology and Pharmaceutical Science 6 11%
Medicine and Dentistry 4 7%
Agricultural and Biological Sciences 3 5%
Other 5 9%
Unknown 19 33%

Attention Score in Context

This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 March 2019.
All research outputs
#4,145,308
of 21,326,488 outputs
Outputs from Journal of Neuroinflammation
#871
of 2,456 outputs
Outputs of similar age
#74,212
of 282,801 outputs
Outputs of similar age from Journal of Neuroinflammation
#2
of 4 outputs
Altmetric has tracked 21,326,488 research outputs across all sources so far. Compared to these this one has done well and is in the 80th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,456 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.1. This one has gotten more attention than average, scoring higher than 64% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 282,801 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 73% of its contemporaries.
We're also able to compare this research output to 4 others from the same source and published within six weeks on either side of this one. This one has scored higher than 2 of them.