P2X7 receptor-activated microglia in cortex is critical for sleep disorder under neuropathic pain
Neuropathic pain (NP) is associated with sleep disturbances, which may substantially influence the quality of life. Clinical and animal studies demonstrated that neurotransmitter is one of the main contributors to cause sleep disturbances induced by NP. Recently, it was reported that P2X7 receptors...
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Frontiers Media S.A.
2023-02-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2023.1095718/full |
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author | Tingting Li Yunling Gao Mengying He Mengying He Zhu Gui Zhu Gui Bingchu Zhao Bingchu Zhao Yue Cao Ting Chen Jinpiao Zhu Jinpiao Zhu Jie Wang Jie Wang Jie Wang Qi Zhong Zongze Zhang |
author_facet | Tingting Li Yunling Gao Mengying He Mengying He Zhu Gui Zhu Gui Bingchu Zhao Bingchu Zhao Yue Cao Ting Chen Jinpiao Zhu Jinpiao Zhu Jie Wang Jie Wang Jie Wang Qi Zhong Zongze Zhang |
author_sort | Tingting Li |
collection | DOAJ |
description | Neuropathic pain (NP) is associated with sleep disturbances, which may substantially influence the quality of life. Clinical and animal studies demonstrated that neurotransmitter is one of the main contributors to cause sleep disturbances induced by NP. Recently, it was reported that P2X7 receptors (P2X7R) are widely expressed in microglia, which serves crucial role in neuronal activity in the pain and sleep-awake cycle. In this study, we adopted the chronic constriction injury (CCI) model to establish the progress of chronic pain and investigated whether P2X7R of microglia in cortex played a critical role in sleep disturbance induced by NP. At electroencephalogram (EEG) level, sleep disturbance was observed in mice treated with CCI as they exhibited mechanical and thermal hypersensitivity, and inhibition of P2X7R ameliorated these changes. We showed a dramatic high level of P2X7R and Iba-1 co-expression in the cortical region, and the inhibition of P2X7R also adversely affected it. Furthermore, the power of LFPs in ventral posterior nucleus (VP) and primary somatosensory cortex (S1) which changed in the CCI group was adverse after the inhibition of P2X7R. Furthermore, inhibition of P2X7R also decreased the VP-S1 coherence which increased in CCI group. Nuclear magnetic resonance demonstrated inhibition of P2X7R decreased glutamate (Glu) levels in thalamic and cortical regions which were significantly increased in the CCI mice. Our findings provide evidence that NP has a critical effect on neuronal activity linked to sleep and may built up a new target for the development of sleep disturbances under chronic pain conditions. |
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spelling | doaj.art-1b40af592e1d4e9793d4eea818d2cac52023-02-03T07:03:25ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2023-02-011710.3389/fnins.2023.10957181095718P2X7 receptor-activated microglia in cortex is critical for sleep disorder under neuropathic painTingting Li0Yunling Gao1Mengying He2Mengying He3Zhu Gui4Zhu Gui5Bingchu Zhao6Bingchu Zhao7Yue Cao8Ting Chen9Jinpiao Zhu10Jinpiao Zhu11Jie Wang12Jie Wang13Jie Wang14Qi Zhong15Zongze Zhang16Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, ChinaXiangyang Central Hospital, Institute of Neuroscience and Brain Diseases, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, ChinaDepartment of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, ChinaKey Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan National Laboratory for Optoelectronics, Wuhan, ChinaKey Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan National Laboratory for Optoelectronics, Wuhan, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaKey Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan National Laboratory for Optoelectronics, Wuhan, ChinaSchool of Computer Science, Wuhan University, Wuhan, Hubei, ChinaDepartment of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, ChinaDepartment of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, ChinaDepartment of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, ChinaKey Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan National Laboratory for Optoelectronics, Wuhan, ChinaXiangyang Central Hospital, Institute of Neuroscience and Brain Diseases, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, ChinaKey Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan National Laboratory for Optoelectronics, Wuhan, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaDepartment of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, ChinaDepartment of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, ChinaNeuropathic pain (NP) is associated with sleep disturbances, which may substantially influence the quality of life. Clinical and animal studies demonstrated that neurotransmitter is one of the main contributors to cause sleep disturbances induced by NP. Recently, it was reported that P2X7 receptors (P2X7R) are widely expressed in microglia, which serves crucial role in neuronal activity in the pain and sleep-awake cycle. In this study, we adopted the chronic constriction injury (CCI) model to establish the progress of chronic pain and investigated whether P2X7R of microglia in cortex played a critical role in sleep disturbance induced by NP. At electroencephalogram (EEG) level, sleep disturbance was observed in mice treated with CCI as they exhibited mechanical and thermal hypersensitivity, and inhibition of P2X7R ameliorated these changes. We showed a dramatic high level of P2X7R and Iba-1 co-expression in the cortical region, and the inhibition of P2X7R also adversely affected it. Furthermore, the power of LFPs in ventral posterior nucleus (VP) and primary somatosensory cortex (S1) which changed in the CCI group was adverse after the inhibition of P2X7R. Furthermore, inhibition of P2X7R also decreased the VP-S1 coherence which increased in CCI group. Nuclear magnetic resonance demonstrated inhibition of P2X7R decreased glutamate (Glu) levels in thalamic and cortical regions which were significantly increased in the CCI mice. Our findings provide evidence that NP has a critical effect on neuronal activity linked to sleep and may built up a new target for the development of sleep disturbances under chronic pain conditions.https://www.frontiersin.org/articles/10.3389/fnins.2023.1095718/fullP2X7Rneuropathic painmicrogliasleep disturbancethalamocortical oscillation |
spellingShingle | Tingting Li Yunling Gao Mengying He Mengying He Zhu Gui Zhu Gui Bingchu Zhao Bingchu Zhao Yue Cao Ting Chen Jinpiao Zhu Jinpiao Zhu Jie Wang Jie Wang Jie Wang Qi Zhong Zongze Zhang P2X7 receptor-activated microglia in cortex is critical for sleep disorder under neuropathic pain Frontiers in Neuroscience P2X7R neuropathic pain microglia sleep disturbance thalamocortical oscillation |
title | P2X7 receptor-activated microglia in cortex is critical for sleep disorder under neuropathic pain |
title_full | P2X7 receptor-activated microglia in cortex is critical for sleep disorder under neuropathic pain |
title_fullStr | P2X7 receptor-activated microglia in cortex is critical for sleep disorder under neuropathic pain |
title_full_unstemmed | P2X7 receptor-activated microglia in cortex is critical for sleep disorder under neuropathic pain |
title_short | P2X7 receptor-activated microglia in cortex is critical for sleep disorder under neuropathic pain |
title_sort | p2x7 receptor activated microglia in cortex is critical for sleep disorder under neuropathic pain |
topic | P2X7R neuropathic pain microglia sleep disturbance thalamocortical oscillation |
url | https://www.frontiersin.org/articles/10.3389/fnins.2023.1095718/full |
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