Different neuronal populations mediate inflammatory pain analgesia by exogenous and endogenous opioids

Abstract

Mu-opioid receptors (MORs) are crucial for analgesia by both exogenous and endogenous opioids. However, the distinct mechanisms underlying these two types of opioid analgesia remains largely unknown. Here, we demonstrate that analgesic effects of exogenous and endogenous opioids on inflammatory pain are mediated by MORs expressed in distinct subpopulations of neurons in mouse. We found that the exogenous opioid-induced analgesia of inflammatory pain is mediated by MORs in Vglut2+ glutamatergic but not GABAergic neurons. In contrast, analgesia by endogenous opioids is mediated by MORs in GABAergic rather than Vglut2+ glutamatergic neurons. Furthermore, MORs expressed at the spinal level is mainly involved in the analgesic effect of morphine in acute pain, but not in endogenous opioid analgesia during chronic inflammatory pain. Thus, our study revealed distinct mechanisms underlying analgesia by exogenous and endogenous opioids, and laid the foundation for further dissecting the circuit mechanism underlying opioid analgesia.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Xin-Yan Zhang

    Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Yan-Nong Dou

    Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9096-6284
  3. Lei Yuan

    Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Qing Li

    Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Yan-Jing Zhu

    Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Meng Wang

    Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Yan-Gang Sun

    Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China
    For correspondence
    yangang.sun@ion.ac.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0768-7733

Funding

Shanghai Municipal Science and Technology Major Project (2018SHZDZX05)

  • Yan-Gang Sun

Chinese Academy of Sciences (XDB32010200)

  • Yan-Gang Sun

China Postdoctoral Science Foundation (2018M640426)

  • Yan-Nong Dou

Shanghai Postdoctoral Excellence Program (2018038)

  • Yan-Nong Dou

National Natural Science Foundation of China (31825013)

  • Yan-Gang Sun

National Natural Science Foundation of China (31800877)

  • Yan-Nong Dou

National Natural Science Foundation of China (61890952)

  • Yan-Gang Sun

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Kate M Wassum, University of California, Los Angeles, United States

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the Institute of Neuroscience, CAS. All procedures were approved by the Animal Care and Use Committee of the Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China (Protocol number: NA-005-2019).

Version history

  1. Received: January 19, 2020
  2. Accepted: June 10, 2020
  3. Accepted Manuscript published: June 10, 2020 (version 1)
  4. Version of Record published: June 23, 2020 (version 2)

Copyright

© 2020, Zhang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Xin-Yan Zhang
  2. Yan-Nong Dou
  3. Lei Yuan
  4. Qing Li
  5. Yan-Jing Zhu
  6. Meng Wang
  7. Yan-Gang Sun
(2020)
Different neuronal populations mediate inflammatory pain analgesia by exogenous and endogenous opioids
eLife 9:e55289.
https://doi.org/10.7554/eLife.55289

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https://doi.org/10.7554/eLife.55289

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