A neural circuit for alcohol withdrawal-induced hyperalgesia in a nondependent state.

Yang, Xin-Lu; Gao, Wei; Dong, Wan-Ying; Zheng, Changjian; Wang, Sheng; Wei, Hong-Rui; Luo, Yanli; Zhang, Zhi et al. · Sci Adv · 2024

basic_science · Level V

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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 (dCA1<sup>Glu</sup>) to anterior cingulate cortex glutamatergic neurons (ACC<sup>Glu</sup>) 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 dCA1<sup>Glu</sup> → ACC<sup>Glu</sup> neuronal pathway participates in driving EW-induced hyperalgesia before ethanol dependence in mice.

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