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Sci Rep. 2019 Nov 5;9(1):16032. doi: 10.1038/s41598-019-52405-0.

Inhibiting the LPS-induced enhancement of mEPSC frequency in superficial dorsal horn neurons may serve as an electrophysiological model for alleviating pain.

Author information

1
School of Chinese Medicine, China Medical University, Taichung, Taiwan.
2
Department of Leisure Industry and Health Promotion, National Ilan University, Yilan, Taiwan.
3
Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
4
Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
5
Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan.
6
Department of Chinese Medicine, China Medical University Hospital, Taipei branch, Taipei, Taiwan.
7
Department of Anesthesiology, National Taiwan University Hospital, Taipei, Taiwan. pll5611@ntu.edu.tw.
8
Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan. yihungchen@mail.cmu.edu.tw.
9
Chinese Medicine Research Center, China Medical University, Taichung, Taiwan. yihungchen@mail.cmu.edu.tw.
10
Department of Photonics and Communication Engineering, Asia University, Taichung, Taiwan. yihungchen@mail.cmu.edu.tw.

Abstract

Pain is a major primary health care problem. Emerging studies show that inhibition of spinal microglial activation reduces pain. However, the precise mechanisms by which microglial activation contributes to nociceptive synaptic transmission remain unclear. In this study, we measured spontaneous synaptic activity of miniature excitatory postsynaptic currents (mEPSCs) in rat spinal cord superficial dorsal horn (SDH, laminae I and II) neurons. Lipopolysaccharide (LPS) and adenosine triphosphate (ATP) increased the frequency, but not amplitude, of mEPSCs in SDH neurons. Microglial inhibitors minocycline and paeonol, as well as an astrocyte inhibitor, a P2Y1 receptor (P2Y1R) antagonist, and a metabotropic glutamate receptor 5 (mGluR5) antagonist, all prevented LPS-induced enhancement of mEPSC frequency. In mouse behavioral testing, minocycline and paeonol effectively reduced acetic acid-induced writhing and LPS-induced hyperalgesia. These results indicate that LPS-activated microglia release ATP, which stimulates astrocyte P2Y1Rs to release glutamate, triggering presynaptic mGluR5 receptors and increasing presynaptic glutamate release, leading to an increase in mEPSC frequency and enhancement of nociceptive transmission in SDH neurons. We propose that these effects can serve as a new electrophysiological model for evaluating pain. Moreover, we predict that pharmacologic agents capable of inhibiting the LPS-induced enhancement of mEPSC frequency in SDH neurons will have analgesic effects.

PMID:
31690742
DOI:
10.1038/s41598-019-52405-0
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