A nigro–subthalamo–parabrachial pathway modulates pain-like behaviors

The basal ganglia including the subthalamic nucleus (STN) and substantia nigra pars reticulata (SNr) are involved in pain-related responses, but how they regulate pain processing remains unknown. Here, we identify a pathway, consisting of GABAergic neurons in the SNr (SNr(GABA)) and glutamatergic ne...

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Autores principales: Jia, Tao, Wang, Ying-Di, Chen, Jing, Zhang, Xue, Cao, Jun-Li, Xiao, Cheng, Zhou, Chunyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9755217/
https://www.ncbi.nlm.nih.gov/pubmed/36522327
http://dx.doi.org/10.1038/s41467-022-35474-0
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author Jia, Tao
Wang, Ying-Di
Chen, Jing
Zhang, Xue
Cao, Jun-Li
Xiao, Cheng
Zhou, Chunyi
author_facet Jia, Tao
Wang, Ying-Di
Chen, Jing
Zhang, Xue
Cao, Jun-Li
Xiao, Cheng
Zhou, Chunyi
author_sort Jia, Tao
collection PubMed
description The basal ganglia including the subthalamic nucleus (STN) and substantia nigra pars reticulata (SNr) are involved in pain-related responses, but how they regulate pain processing remains unknown. Here, we identify a pathway, consisting of GABAergic neurons in the SNr (SNr(GABA)) and glutamatergic neurons in the STN (STN(Glu)) and the lateral parabrachial nucleus (LPB(Glu)), that modulates acute and persistent pain states in both male and female mice. The activity of STN neurons was enhanced in acute and persistent pain states. This enhancement was accompanied by hypoactivity in SNr(GABA) neurons and strengthening of the STN–LPB glutamatergic projection. Reversing the dysfunction in the SNr(GABA)-STN(Glu)-LPB(Glu) pathway attenuated activity of LPB(Glu) neurons and mitigated pain-like behaviors. Therefore, the SNr(GABA)-STN(Glu)-LPB(Glu) pathway regulates pathological pain and is a potential target for pain management.
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spelling pubmed-97552172022-12-17 A nigro–subthalamo–parabrachial pathway modulates pain-like behaviors Jia, Tao Wang, Ying-Di Chen, Jing Zhang, Xue Cao, Jun-Li Xiao, Cheng Zhou, Chunyi Nat Commun Article The basal ganglia including the subthalamic nucleus (STN) and substantia nigra pars reticulata (SNr) are involved in pain-related responses, but how they regulate pain processing remains unknown. Here, we identify a pathway, consisting of GABAergic neurons in the SNr (SNr(GABA)) and glutamatergic neurons in the STN (STN(Glu)) and the lateral parabrachial nucleus (LPB(Glu)), that modulates acute and persistent pain states in both male and female mice. The activity of STN neurons was enhanced in acute and persistent pain states. This enhancement was accompanied by hypoactivity in SNr(GABA) neurons and strengthening of the STN–LPB glutamatergic projection. Reversing the dysfunction in the SNr(GABA)-STN(Glu)-LPB(Glu) pathway attenuated activity of LPB(Glu) neurons and mitigated pain-like behaviors. Therefore, the SNr(GABA)-STN(Glu)-LPB(Glu) pathway regulates pathological pain and is a potential target for pain management. Nature Publishing Group UK 2022-12-15 /pmc/articles/PMC9755217/ /pubmed/36522327 http://dx.doi.org/10.1038/s41467-022-35474-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Jia, Tao
Wang, Ying-Di
Chen, Jing
Zhang, Xue
Cao, Jun-Li
Xiao, Cheng
Zhou, Chunyi
A nigro–subthalamo–parabrachial pathway modulates pain-like behaviors
title A nigro–subthalamo–parabrachial pathway modulates pain-like behaviors
title_full A nigro–subthalamo–parabrachial pathway modulates pain-like behaviors
title_fullStr A nigro–subthalamo–parabrachial pathway modulates pain-like behaviors
title_full_unstemmed A nigro–subthalamo–parabrachial pathway modulates pain-like behaviors
title_short A nigro–subthalamo–parabrachial pathway modulates pain-like behaviors
title_sort nigro–subthalamo–parabrachial pathway modulates pain-like behaviors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9755217/
https://www.ncbi.nlm.nih.gov/pubmed/36522327
http://dx.doi.org/10.1038/s41467-022-35474-0
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