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A TRPV4-dependent neuroimmune axis in the spinal cord promotes neuropathic pain
Microglia, resident macrophages of the CNS, are essential to brain development, homeostasis, and disease. Microglial activation and proliferation are hallmarks of many CNS diseases, including neuropathic pain. However, molecular mechanisms that govern the spinal neuroimmune axis in the setting of ne...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9974096/ https://www.ncbi.nlm.nih.gov/pubmed/36701202 http://dx.doi.org/10.1172/JCI161507 |
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author | Hu, Xueming Du, Lixia Liu, Shenbin Lan, Zhou Zang, Kaikai Feng, Jing Zhao, Yonghui Yang, Xingliang Xie, Zili Wang, Peter L. Ver Heul, Aaron M. Chen, Lvyi Samineni, Vijay K. Wang, Yan-Qing Lavine, Kory J. Gereau, Robert W. Wu, Gregory F. Hu, Hongzhen |
author_facet | Hu, Xueming Du, Lixia Liu, Shenbin Lan, Zhou Zang, Kaikai Feng, Jing Zhao, Yonghui Yang, Xingliang Xie, Zili Wang, Peter L. Ver Heul, Aaron M. Chen, Lvyi Samineni, Vijay K. Wang, Yan-Qing Lavine, Kory J. Gereau, Robert W. Wu, Gregory F. Hu, Hongzhen |
author_sort | Hu, Xueming |
collection | PubMed |
description | Microglia, resident macrophages of the CNS, are essential to brain development, homeostasis, and disease. Microglial activation and proliferation are hallmarks of many CNS diseases, including neuropathic pain. However, molecular mechanisms that govern the spinal neuroimmune axis in the setting of neuropathic pain remain incompletely understood. Here, we show that genetic ablation or pharmacological blockade of transient receptor potential vanilloid type 4 (TRPV4) markedly attenuated neuropathic pain-like behaviors in a mouse model of spared nerve injury. Mechanistically, microglia-expressed TRPV4 mediated microglial activation and proliferation and promoted functional and structural plasticity of excitatory spinal neurons through release of lipocalin-2. Our results suggest that microglial TRPV4 channels reside at the center of the neuroimmune axis in the spinal cord, which transforms peripheral nerve injury into central sensitization and neuropathic pain, thereby identifying TRPV4 as a potential new target for the treatment of chronic pain. |
format | Online Article Text |
id | pubmed-9974096 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-99740962023-03-01 A TRPV4-dependent neuroimmune axis in the spinal cord promotes neuropathic pain Hu, Xueming Du, Lixia Liu, Shenbin Lan, Zhou Zang, Kaikai Feng, Jing Zhao, Yonghui Yang, Xingliang Xie, Zili Wang, Peter L. Ver Heul, Aaron M. Chen, Lvyi Samineni, Vijay K. Wang, Yan-Qing Lavine, Kory J. Gereau, Robert W. Wu, Gregory F. Hu, Hongzhen J Clin Invest Research Article Microglia, resident macrophages of the CNS, are essential to brain development, homeostasis, and disease. Microglial activation and proliferation are hallmarks of many CNS diseases, including neuropathic pain. However, molecular mechanisms that govern the spinal neuroimmune axis in the setting of neuropathic pain remain incompletely understood. Here, we show that genetic ablation or pharmacological blockade of transient receptor potential vanilloid type 4 (TRPV4) markedly attenuated neuropathic pain-like behaviors in a mouse model of spared nerve injury. Mechanistically, microglia-expressed TRPV4 mediated microglial activation and proliferation and promoted functional and structural plasticity of excitatory spinal neurons through release of lipocalin-2. Our results suggest that microglial TRPV4 channels reside at the center of the neuroimmune axis in the spinal cord, which transforms peripheral nerve injury into central sensitization and neuropathic pain, thereby identifying TRPV4 as a potential new target for the treatment of chronic pain. American Society for Clinical Investigation 2023-03-01 /pmc/articles/PMC9974096/ /pubmed/36701202 http://dx.doi.org/10.1172/JCI161507 Text en © 2023 Hu et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Hu, Xueming Du, Lixia Liu, Shenbin Lan, Zhou Zang, Kaikai Feng, Jing Zhao, Yonghui Yang, Xingliang Xie, Zili Wang, Peter L. Ver Heul, Aaron M. Chen, Lvyi Samineni, Vijay K. Wang, Yan-Qing Lavine, Kory J. Gereau, Robert W. Wu, Gregory F. Hu, Hongzhen A TRPV4-dependent neuroimmune axis in the spinal cord promotes neuropathic pain |
title | A TRPV4-dependent neuroimmune axis in the spinal cord promotes neuropathic pain |
title_full | A TRPV4-dependent neuroimmune axis in the spinal cord promotes neuropathic pain |
title_fullStr | A TRPV4-dependent neuroimmune axis in the spinal cord promotes neuropathic pain |
title_full_unstemmed | A TRPV4-dependent neuroimmune axis in the spinal cord promotes neuropathic pain |
title_short | A TRPV4-dependent neuroimmune axis in the spinal cord promotes neuropathic pain |
title_sort | trpv4-dependent neuroimmune axis in the spinal cord promotes neuropathic pain |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9974096/ https://www.ncbi.nlm.nih.gov/pubmed/36701202 http://dx.doi.org/10.1172/JCI161507 |
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