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Updated: Jun 11, 2025

Investigating Drivers of Antireward in Addiction Behavior with Anatomically Specific Single-Cell Gene Expression Methods
Published on: August 4, 2022
A neural circuit for alcohol withdrawal-induced hyperalgesia in a nondependent state
Xin-Lu Yang1,2, Wei Gao1, Wan-Ying Dong1
1Department of Anesthesiology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
Abstract:
Alcohol use disorder is highly prevalent worldwide, with characteristically severe pain sensitivity during withdrawal. Here, we established a mouse model of hyperalgesia during ethanol withdrawal (EW) before addiction to investigate the window for onset and underlying mechanisms. Viral tracing with in vivo microendoscopic and two-photon calcium imaging identified a circuit pathway from dorsal hippocampal CA1 glutamatergic neurons (dCA1Glu) to anterior cingulate cortex glutamatergic neurons (ACCGlu) activated in EW mice with hyperalgesia. Chemogenetic inhibition of this pathway can alleviate hyperalgesia in EW mice, whereas artificial activation recapitulates EW-induced hyperalgesia in naïve mice. These findings demonstrate that the dCA1Glu → ACCGlu neuronal pathway participates in driving EW-induced hyperalgesia before ethanol dependence in mice.
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