A microglial activation cascade across cortical regions underlies secondary mechanical hypersensitivity to amputation
Summary: Neural mechanisms underlying amputation-related secondary pain are unclear. Using in vivo two-photon imaging, three-dimensional reconstruction, and fiber photometry recording, we show that a microglial activation cascade from the primary somatosensory cortex of forelimb (S1FL) to the primar...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724001323 |
| _version_ | 1797291807419138048 |
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| author | Hong-Rui Wei Lan Tang Xin-Lu Yang Chang-Mao Chen Le-Xian Li Yu Mao Di Wang Fang Kang Sen Qun Zhi Zhang Peng Cao Yan Jin |
| author_facet | Hong-Rui Wei Lan Tang Xin-Lu Yang Chang-Mao Chen Le-Xian Li Yu Mao Di Wang Fang Kang Sen Qun Zhi Zhang Peng Cao Yan Jin |
| author_sort | Hong-Rui Wei |
| collection | DOAJ |
| description | Summary: Neural mechanisms underlying amputation-related secondary pain are unclear. Using in vivo two-photon imaging, three-dimensional reconstruction, and fiber photometry recording, we show that a microglial activation cascade from the primary somatosensory cortex of forelimb (S1FL) to the primary somatosensory cortex of hindlimb (S1HL) mediates the disinhibition and subsequent hyperexcitation of glutamatergic neurons in the S1HL (S1HLGlu), which then drives secondary mechanical hypersensitivity development in ipsilateral hindpaws of mice with forepaw amputation. Forepaw amputation induces rapid S1FL microglial activation that further activates S1HL microglia via the CCL2-CCR2 signaling pathway. Increased engulfment of GABAergic presynapses by activated microglia stimulates S1HLGlu neuronal activity, ultimately leading to secondary mechanical hypersensitivity of hindpaws. It is widely believed direct neuronal projection drives interactions between distinct brain regions to prime specific behaviors. Our study reveals microglial interactions spanning different subregions of the somatosensory cortex to drive a maladaptive neuronal response underlying secondary mechanical hypersensitivity at non-injured sites. |
| first_indexed | 2024-03-07T19:43:05Z |
| format | Article |
| id | doaj.art-fe258a5b16c04adc9efd82f212ec5125 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-07T19:43:05Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-fe258a5b16c04adc9efd82f212ec51252024-02-29T05:19:01ZengElsevierCell Reports2211-12472024-02-01432113804A microglial activation cascade across cortical regions underlies secondary mechanical hypersensitivity to amputationHong-Rui Wei0Lan Tang1Xin-Lu Yang2Chang-Mao Chen3Le-Xian Li4Yu Mao5Di Wang6Fang Kang7Sen Qun8Zhi Zhang9Peng Cao10Yan Jin11Department of Anesthesiology, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; Department of Anesthesiology, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui 241000, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, ChinaStroke Center and Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; Center for Advanced Interdisciplinary Science and Biomedicine, Institute of Health and Medicine, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; Corresponding authorStroke Center and Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; Corresponding authorStroke Center and Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; Corresponding authorSummary: Neural mechanisms underlying amputation-related secondary pain are unclear. Using in vivo two-photon imaging, three-dimensional reconstruction, and fiber photometry recording, we show that a microglial activation cascade from the primary somatosensory cortex of forelimb (S1FL) to the primary somatosensory cortex of hindlimb (S1HL) mediates the disinhibition and subsequent hyperexcitation of glutamatergic neurons in the S1HL (S1HLGlu), which then drives secondary mechanical hypersensitivity development in ipsilateral hindpaws of mice with forepaw amputation. Forepaw amputation induces rapid S1FL microglial activation that further activates S1HL microglia via the CCL2-CCR2 signaling pathway. Increased engulfment of GABAergic presynapses by activated microglia stimulates S1HLGlu neuronal activity, ultimately leading to secondary mechanical hypersensitivity of hindpaws. It is widely believed direct neuronal projection drives interactions between distinct brain regions to prime specific behaviors. Our study reveals microglial interactions spanning different subregions of the somatosensory cortex to drive a maladaptive neuronal response underlying secondary mechanical hypersensitivity at non-injured sites.http://www.sciencedirect.com/science/article/pii/S2211124724001323CP: Neuroscience |
| spellingShingle | Hong-Rui Wei Lan Tang Xin-Lu Yang Chang-Mao Chen Le-Xian Li Yu Mao Di Wang Fang Kang Sen Qun Zhi Zhang Peng Cao Yan Jin A microglial activation cascade across cortical regions underlies secondary mechanical hypersensitivity to amputation Cell Reports CP: Neuroscience |
| title | A microglial activation cascade across cortical regions underlies secondary mechanical hypersensitivity to amputation |
| title_full | A microglial activation cascade across cortical regions underlies secondary mechanical hypersensitivity to amputation |
| title_fullStr | A microglial activation cascade across cortical regions underlies secondary mechanical hypersensitivity to amputation |
| title_full_unstemmed | A microglial activation cascade across cortical regions underlies secondary mechanical hypersensitivity to amputation |
| title_short | A microglial activation cascade across cortical regions underlies secondary mechanical hypersensitivity to amputation |
| title_sort | microglial activation cascade across cortical regions underlies secondary mechanical hypersensitivity to amputation |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724001323 |
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