Different neuronal populations mediate inflammatory pain analgesia by exogenous and endogenous opioids
- Chinese Academy of Sciences, China
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.
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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.
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).
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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Different neuronal populations mediate inflammatory pain analgesia by exogenous and endogenous opioids
eLife 9:e55289.
https://doi.org/10.7554/eLife.55289
