TY - JOUR
T1 - Highly synchronized cortical circuit dynamics mediate spontaneous pain in mice
AU - Ding, Weihua
AU - Fischer, Lukas
AU - Chen, Qian
AU - Li, Ziyi
AU - Yang, Liuyue
AU - You, Zerong
AU - Hu, Kun
AU - Wu, Xinbo
AU - Zhou, Xue
AU - Chao, Wei
AU - Hu, Peter
AU - Dagnew, Tewodros Mulugeta
AU - Dubreuil, Daniel M.
AU - Wang, Shiyu
AU - Xia, Suyun
AU - Bao, Caroline
AU - Zhu, Shengmei
AU - Chen, Lucy
AU - Wang, Changning
AU - Wainger, Brian
AU - Jin, Peng
AU - Mao, Jianren
AU - Feng, Guoping
AU - Harnett, Mark T.
AU - Shen, Shiqian
N1 - Publisher Copyright:
© 2023 American Society for Clinical Investigation. All rights reserved.
PY - 2023/3/1
Y1 - 2023/3/1
N2 - 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.
AB - 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.
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U2 - 10.1172/JCI166408
DO - 10.1172/JCI166408
M3 - Article
C2 - 36602876
AN - SCOPUS:85149153937
SN - 0021-9738
VL - 133
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 5
M1 - :e166408. 10.1172/JCI166408
ER -