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Spinal microglia contribute to sustained inflammatory pain via amplifying neuronal activity
Microglia are highly dynamic immune cells of the central nervous system (CNS). Microglial processes interact with neuronal elements constantly on the order of minutes. The functional significance of this acute microglia-neuron interaction and its potential role in the context of pain is still largel...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9609165/ https://www.ncbi.nlm.nih.gov/pubmed/36289499 http://dx.doi.org/10.1186/s13041-022-00970-3 |
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author | Gu, Nan Yi, Min-Hee Murugan, Madhuvika Xie, Manling Parusel, Sebastian Peng, Jiyun Eyo, Ukpong B. Hunt, Christine L. Dong, Hailong Wu, Long-Jun |
author_facet | Gu, Nan Yi, Min-Hee Murugan, Madhuvika Xie, Manling Parusel, Sebastian Peng, Jiyun Eyo, Ukpong B. Hunt, Christine L. Dong, Hailong Wu, Long-Jun |
author_sort | Gu, Nan |
collection | PubMed |
description | Microglia are highly dynamic immune cells of the central nervous system (CNS). Microglial processes interact with neuronal elements constantly on the order of minutes. The functional significance of this acute microglia-neuron interaction and its potential role in the context of pain is still largely unknown. Here, we found that spinal microglia increased their process motility and electrophysiological reactivity within an hour after the insult in a mouse model of formalin-induced acute, sustained, inflammatory pain. Using an ablation strategy to specifically deplete resident microglia in the CNS, we demonstrate that microglia participate in formalin-induced acute sustained pain behaviors by amplifying neuronal activity in the spinal dorsal horn. Moreover, we identified that the P2Y12 receptor, which is specifically expressed in microglia in the CNS, was required for microglial function in formalin-induced pain. Taken together, our study provides a novel insight into the contribution of microglia and the P2Y12 receptor in inflammatory pain that could be used for potential therapeutic strategies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13041-022-00970-3. |
format | Online Article Text |
id | pubmed-9609165 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-96091652022-10-28 Spinal microglia contribute to sustained inflammatory pain via amplifying neuronal activity Gu, Nan Yi, Min-Hee Murugan, Madhuvika Xie, Manling Parusel, Sebastian Peng, Jiyun Eyo, Ukpong B. Hunt, Christine L. Dong, Hailong Wu, Long-Jun Mol Brain Research Microglia are highly dynamic immune cells of the central nervous system (CNS). Microglial processes interact with neuronal elements constantly on the order of minutes. The functional significance of this acute microglia-neuron interaction and its potential role in the context of pain is still largely unknown. Here, we found that spinal microglia increased their process motility and electrophysiological reactivity within an hour after the insult in a mouse model of formalin-induced acute, sustained, inflammatory pain. Using an ablation strategy to specifically deplete resident microglia in the CNS, we demonstrate that microglia participate in formalin-induced acute sustained pain behaviors by amplifying neuronal activity in the spinal dorsal horn. Moreover, we identified that the P2Y12 receptor, which is specifically expressed in microglia in the CNS, was required for microglial function in formalin-induced pain. Taken together, our study provides a novel insight into the contribution of microglia and the P2Y12 receptor in inflammatory pain that could be used for potential therapeutic strategies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13041-022-00970-3. BioMed Central 2022-10-26 /pmc/articles/PMC9609165/ /pubmed/36289499 http://dx.doi.org/10.1186/s13041-022-00970-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Gu, Nan Yi, Min-Hee Murugan, Madhuvika Xie, Manling Parusel, Sebastian Peng, Jiyun Eyo, Ukpong B. Hunt, Christine L. Dong, Hailong Wu, Long-Jun Spinal microglia contribute to sustained inflammatory pain via amplifying neuronal activity |
title | Spinal microglia contribute to sustained inflammatory pain via amplifying neuronal activity |
title_full | Spinal microglia contribute to sustained inflammatory pain via amplifying neuronal activity |
title_fullStr | Spinal microglia contribute to sustained inflammatory pain via amplifying neuronal activity |
title_full_unstemmed | Spinal microglia contribute to sustained inflammatory pain via amplifying neuronal activity |
title_short | Spinal microglia contribute to sustained inflammatory pain via amplifying neuronal activity |
title_sort | spinal microglia contribute to sustained inflammatory pain via amplifying neuronal activity |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9609165/ https://www.ncbi.nlm.nih.gov/pubmed/36289499 http://dx.doi.org/10.1186/s13041-022-00970-3 |
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