1. Highly synchronized cortical circuit dynamics mediate spontaneous pain in mice
- Author
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Ding, Weihua, Fischer, Lukas, Chen, Qian, Li, Ziyi, Yang, Liuyue, You, Zerong, Hu, Kun, Wu, Xinbo, Zhou, Xue, Chao, Wei, Hu, Peter, Dagnew, Tewodros Mulugeta, Dubreuil, Daniel M., Wang, Shiyu, Xia, Suyun, Bao, Caroline, Zhu, Shengmei, Chen, Lucy, Wang, Changning, Wainger, Brian, Jin, Peng, Mao, Jianren, Feng, Guoping, Harnet, Mark T., and Shen, Shiqian
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Neural circuitry -- Health aspects ,Orofacial pain -- Development and progression ,Facial pain -- Development and progression ,Neural oscillations -- Health aspects ,Health care industry - Abstract
Cortical neural dynamics mediate information processing for the cerebral cortex, which is implicated in fundamental biological processes such as vision and olfaction, in addition to neurological and psychiatric diseases. Spontaneous pain is a key feature of human neuropathic pain. Whether spontaneous pain pushes the cortical network into an aberrant state and, if so, whether it can be brought back to a 'normal' operating range to ameliorate pain are unknown. Using a clinically relevant mouse model of neuropathic pain with spontaneous pain-like behavior, we report that orofacial spontaneous pain activated a specific area within the primary somatosensory cortex (S1), displaying synchronized neural dynamics revealed by intravital two-photon calcium imaging. This synchronization was underpinned by local GABAergic interneuron hypoactivity. Pain-induced cortical synchronization could be attenuated by manipulating local S1 networks or clinically effective pain therapies. Specifically, both chemogenetic inhibition of pain-related c-Fos-expressing neurons and selective activation of GABAergic interneurons significantly attenuated S1 synchronization. Clinically effective pain therapies including carbamazepine and nerve root decompression could also dampen S1 synchronization. More important, restoring a 'normal' range of neural dynamics through attenuation of pain-induced S1 synchronization alleviated pain-like behavior. These results suggest that spontaneous pain pushed the S1 regional network into a synchronized state, whereas reversal of this synchronization alleviated pain., Introduction Although the functions of cortical circuits vary dramatically between brain regions and species, general principles have been found that constrain neural dynamics to stable activity regimes. For example, sleep, [...]
- Published
- 2023
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