Highly synchronized cortical circuit dynamics mediate spontaneous pain in mice
Name
166408.2-20230227124314-covered-e0fd13ba177f913fd3156f593ead4cfd.pdf
Description
Published version
Size
12.32 MB
Format
Adobe PDF
Checksum (MD5)
000b9fa7eb0b512d7b98ba5c69b9fac1
Author(s)
Ding, Weihua
Fischer, Lukas
Chen, Qian
Li, Ziyi
Yang, Liuyue
You, Zerong
Hu, Kun
Wu, Xinbo
Zhou, Xue
Chao, Wei
Date Issued
March 1, 2023
Journal
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Citation
Ding, Weihua, Fischer, Lukas, Chen, Qian, Li, Ziyi, Yang, Liuyue et al. 2023. "Highly synchronized cortical circuit dynamics mediate spontaneous pain in mice." Journal of Clinical Investigation, 133 (5).
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1172/jci166408
