Cargando…
Deactivation of excitatory neurons in the prelimbic cortex via Cdk5 promotes pain sensation and anxiety
The medial prefrontal cortex (mPFC) is implicated in processing sensory-discriminative and affective pain. Nonetheless, the underlying mechanisms are poorly understood. Here we demonstrate a role for excitatory neurons in the prelimbic cortex (PL), a sub-region of mPFC, in the regulation of pain sen...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518290/ https://www.ncbi.nlm.nih.gov/pubmed/26179626 http://dx.doi.org/10.1038/ncomms8660 |
_version_ | 1782383321438748672 |
---|---|
author | Wang, Guo-Qiang Cen, Cheng Li, Chong Cao, Shuai Wang, Ning Zhou, Zheng Liu, Xue-Mei Xu, Yu Tian, Na-Xi Zhang, Ying Wang, Jun Wang, Li-Ping Wang, Yun |
author_facet | Wang, Guo-Qiang Cen, Cheng Li, Chong Cao, Shuai Wang, Ning Zhou, Zheng Liu, Xue-Mei Xu, Yu Tian, Na-Xi Zhang, Ying Wang, Jun Wang, Li-Ping Wang, Yun |
author_sort | Wang, Guo-Qiang |
collection | PubMed |
description | The medial prefrontal cortex (mPFC) is implicated in processing sensory-discriminative and affective pain. Nonetheless, the underlying mechanisms are poorly understood. Here we demonstrate a role for excitatory neurons in the prelimbic cortex (PL), a sub-region of mPFC, in the regulation of pain sensation and anxiety-like behaviours. Using a chronic inflammatory pain model, we show that lesion of the PL contralateral but not ipsilateral to the inflamed paw attenuates hyperalgesia and anxiety-like behaviours in rats. Optogenetic activation of contralateral PL excitatory neurons exerts analgesic and anxiolytic effects in mice subjected to chronic pain, whereas inhibition is anxiogenic in naive mice. The intrinsic excitability of contralateral PL excitatory neurons is decreased in chronic pain rats; knocking down cyclin-dependent kinase 5 reverses this deactivation and alleviates behavioural impairments. Together, our findings provide novel insights into the role of PL excitatory neurons in the regulation of sensory and affective pain. |
format | Online Article Text |
id | pubmed-4518290 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45182902015-08-07 Deactivation of excitatory neurons in the prelimbic cortex via Cdk5 promotes pain sensation and anxiety Wang, Guo-Qiang Cen, Cheng Li, Chong Cao, Shuai Wang, Ning Zhou, Zheng Liu, Xue-Mei Xu, Yu Tian, Na-Xi Zhang, Ying Wang, Jun Wang, Li-Ping Wang, Yun Nat Commun Article The medial prefrontal cortex (mPFC) is implicated in processing sensory-discriminative and affective pain. Nonetheless, the underlying mechanisms are poorly understood. Here we demonstrate a role for excitatory neurons in the prelimbic cortex (PL), a sub-region of mPFC, in the regulation of pain sensation and anxiety-like behaviours. Using a chronic inflammatory pain model, we show that lesion of the PL contralateral but not ipsilateral to the inflamed paw attenuates hyperalgesia and anxiety-like behaviours in rats. Optogenetic activation of contralateral PL excitatory neurons exerts analgesic and anxiolytic effects in mice subjected to chronic pain, whereas inhibition is anxiogenic in naive mice. The intrinsic excitability of contralateral PL excitatory neurons is decreased in chronic pain rats; knocking down cyclin-dependent kinase 5 reverses this deactivation and alleviates behavioural impairments. Together, our findings provide novel insights into the role of PL excitatory neurons in the regulation of sensory and affective pain. Nature Publishing Group 2015-07-16 /pmc/articles/PMC4518290/ /pubmed/26179626 http://dx.doi.org/10.1038/ncomms8660 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Wang, Guo-Qiang Cen, Cheng Li, Chong Cao, Shuai Wang, Ning Zhou, Zheng Liu, Xue-Mei Xu, Yu Tian, Na-Xi Zhang, Ying Wang, Jun Wang, Li-Ping Wang, Yun Deactivation of excitatory neurons in the prelimbic cortex via Cdk5 promotes pain sensation and anxiety |
title | Deactivation of excitatory neurons in the prelimbic cortex via Cdk5 promotes pain sensation and anxiety |
title_full | Deactivation of excitatory neurons in the prelimbic cortex via Cdk5 promotes pain sensation and anxiety |
title_fullStr | Deactivation of excitatory neurons in the prelimbic cortex via Cdk5 promotes pain sensation and anxiety |
title_full_unstemmed | Deactivation of excitatory neurons in the prelimbic cortex via Cdk5 promotes pain sensation and anxiety |
title_short | Deactivation of excitatory neurons in the prelimbic cortex via Cdk5 promotes pain sensation and anxiety |
title_sort | deactivation of excitatory neurons in the prelimbic cortex via cdk5 promotes pain sensation and anxiety |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518290/ https://www.ncbi.nlm.nih.gov/pubmed/26179626 http://dx.doi.org/10.1038/ncomms8660 |
work_keys_str_mv | AT wangguoqiang deactivationofexcitatoryneuronsintheprelimbiccortexviacdk5promotespainsensationandanxiety AT cencheng deactivationofexcitatoryneuronsintheprelimbiccortexviacdk5promotespainsensationandanxiety AT lichong deactivationofexcitatoryneuronsintheprelimbiccortexviacdk5promotespainsensationandanxiety AT caoshuai deactivationofexcitatoryneuronsintheprelimbiccortexviacdk5promotespainsensationandanxiety AT wangning deactivationofexcitatoryneuronsintheprelimbiccortexviacdk5promotespainsensationandanxiety AT zhouzheng deactivationofexcitatoryneuronsintheprelimbiccortexviacdk5promotespainsensationandanxiety AT liuxuemei deactivationofexcitatoryneuronsintheprelimbiccortexviacdk5promotespainsensationandanxiety AT xuyu deactivationofexcitatoryneuronsintheprelimbiccortexviacdk5promotespainsensationandanxiety AT tiannaxi deactivationofexcitatoryneuronsintheprelimbiccortexviacdk5promotespainsensationandanxiety AT zhangying deactivationofexcitatoryneuronsintheprelimbiccortexviacdk5promotespainsensationandanxiety AT wangjun deactivationofexcitatoryneuronsintheprelimbiccortexviacdk5promotespainsensationandanxiety AT wangliping deactivationofexcitatoryneuronsintheprelimbiccortexviacdk5promotespainsensationandanxiety AT wangyun deactivationofexcitatoryneuronsintheprelimbiccortexviacdk5promotespainsensationandanxiety |