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G protein‐coupled estrogen receptor in the rostral ventromedial medulla contributes to the chronification of postoperative pain
AIMS: Chronification of postoperative pain is a common clinical phenomenon following surgical operation, and it perplexes a great number of patients. Estrogen and its membrane receptor (G protein‐coupled estrogen receptor, GPER) play a crucial role in pain regulation. Here, we explored the role of G...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504531/ https://www.ncbi.nlm.nih.gov/pubmed/34255932 http://dx.doi.org/10.1111/cns.13704 |
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author | Xu, Jia‐Jia Gao, Po Wu, Ying Yin, Su‐Qing Zhu, Ling Xu, Sai‐Hong Tang, Dan Cheung, Chi‐Wai Jiao, Ying‐Fu Yu, Wei‐Feng Li, Yuan‐Hai Yang, Li‐Qun |
author_facet | Xu, Jia‐Jia Gao, Po Wu, Ying Yin, Su‐Qing Zhu, Ling Xu, Sai‐Hong Tang, Dan Cheung, Chi‐Wai Jiao, Ying‐Fu Yu, Wei‐Feng Li, Yuan‐Hai Yang, Li‐Qun |
author_sort | Xu, Jia‐Jia |
collection | PubMed |
description | AIMS: Chronification of postoperative pain is a common clinical phenomenon following surgical operation, and it perplexes a great number of patients. Estrogen and its membrane receptor (G protein‐coupled estrogen receptor, GPER) play a crucial role in pain regulation. Here, we explored the role of GPER in the rostral ventromedial medulla (RVM) during chronic postoperative pain and search for the possible mechanism. METHODS AND RESULTS: Postoperative pain was induced in mice or rats via a plantar incision surgery. Behavioral tests were conducted to detect both thermal and mechanical pain, showing a small part (16.2%) of mice developed into pain persisting state with consistent low pain threshold on 14 days after incision surgery compared with the pain recovery mice. Immunofluorescent staining assay revealed that the GPER‐positive neurons in the RVM were significantly activated in pain persisting rats. In addition, RT‐PCR and immunoblot analyses showed that the levels of GPER and phosphorylated μ‐type opioid receptor (p‐MOR) in the RVM of pain persisting mice were apparently increased on 14 days after incision surgery. Furthermore, chemogenetic activation of GPER‐positive neurons in the RVM of Gper‐Cre mice could reverse the pain threshold of pain recovery mice. Conversely, chemogenetic inhibition of GPER‐positive neurons in the RVM could prevent mice from being in the pain persistent state. CONCLUSION: Our findings demonstrated that the GPER in the RVM was responsible for the chronification of postoperative pain and the downstream pathway might be involved in MOR phosphorylation. |
format | Online Article Text |
id | pubmed-8504531 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85045312021-10-18 G protein‐coupled estrogen receptor in the rostral ventromedial medulla contributes to the chronification of postoperative pain Xu, Jia‐Jia Gao, Po Wu, Ying Yin, Su‐Qing Zhu, Ling Xu, Sai‐Hong Tang, Dan Cheung, Chi‐Wai Jiao, Ying‐Fu Yu, Wei‐Feng Li, Yuan‐Hai Yang, Li‐Qun CNS Neurosci Ther Original Articles AIMS: Chronification of postoperative pain is a common clinical phenomenon following surgical operation, and it perplexes a great number of patients. Estrogen and its membrane receptor (G protein‐coupled estrogen receptor, GPER) play a crucial role in pain regulation. Here, we explored the role of GPER in the rostral ventromedial medulla (RVM) during chronic postoperative pain and search for the possible mechanism. METHODS AND RESULTS: Postoperative pain was induced in mice or rats via a plantar incision surgery. Behavioral tests were conducted to detect both thermal and mechanical pain, showing a small part (16.2%) of mice developed into pain persisting state with consistent low pain threshold on 14 days after incision surgery compared with the pain recovery mice. Immunofluorescent staining assay revealed that the GPER‐positive neurons in the RVM were significantly activated in pain persisting rats. In addition, RT‐PCR and immunoblot analyses showed that the levels of GPER and phosphorylated μ‐type opioid receptor (p‐MOR) in the RVM of pain persisting mice were apparently increased on 14 days after incision surgery. Furthermore, chemogenetic activation of GPER‐positive neurons in the RVM of Gper‐Cre mice could reverse the pain threshold of pain recovery mice. Conversely, chemogenetic inhibition of GPER‐positive neurons in the RVM could prevent mice from being in the pain persistent state. CONCLUSION: Our findings demonstrated that the GPER in the RVM was responsible for the chronification of postoperative pain and the downstream pathway might be involved in MOR phosphorylation. John Wiley and Sons Inc. 2021-07-13 /pmc/articles/PMC8504531/ /pubmed/34255932 http://dx.doi.org/10.1111/cns.13704 Text en © 2021 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Xu, Jia‐Jia Gao, Po Wu, Ying Yin, Su‐Qing Zhu, Ling Xu, Sai‐Hong Tang, Dan Cheung, Chi‐Wai Jiao, Ying‐Fu Yu, Wei‐Feng Li, Yuan‐Hai Yang, Li‐Qun G protein‐coupled estrogen receptor in the rostral ventromedial medulla contributes to the chronification of postoperative pain |
title | G protein‐coupled estrogen receptor in the rostral ventromedial medulla contributes to the chronification of postoperative pain |
title_full | G protein‐coupled estrogen receptor in the rostral ventromedial medulla contributes to the chronification of postoperative pain |
title_fullStr | G protein‐coupled estrogen receptor in the rostral ventromedial medulla contributes to the chronification of postoperative pain |
title_full_unstemmed | G protein‐coupled estrogen receptor in the rostral ventromedial medulla contributes to the chronification of postoperative pain |
title_short | G protein‐coupled estrogen receptor in the rostral ventromedial medulla contributes to the chronification of postoperative pain |
title_sort | g protein‐coupled estrogen receptor in the rostral ventromedial medulla contributes to the chronification of postoperative pain |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504531/ https://www.ncbi.nlm.nih.gov/pubmed/34255932 http://dx.doi.org/10.1111/cns.13704 |
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