Department of Anesthesiology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
Department of Anesthesiology, First Affiliated Hospital of Wannan Medical College, Wuhu 241002, China.
Sci Adv. 2024 Sep 27;10(39):eadp8636. doi: 10.1126/sciadv.adp8636.
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) to anterior cingulate cortex glutamatergic neurons (ACC) 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 → ACC neuronal pathway participates in driving EW-induced hyperalgesia before ethanol dependence in mice.
酒精使用障碍在全球范围内高发，戒断时通常会出现严重的疼痛敏感性。在这里，我们建立了一个乙醇戒断（EW）期间痛觉过敏的小鼠模型，以研究发病窗口和潜在机制。通过体内显微镜和双光子钙成像的病毒追踪，鉴定出一个从背侧海马 CA1 谷氨酸能神经元（dCA1）到前扣带皮层谷氨酸能神经元（ACC）的回路途径，在有痛觉过敏的 EW 小鼠中被激活。该通路的化学遗传抑制可以减轻 EW 小鼠的痛觉过敏，而人工激活则可在无经验的小鼠中再现 EW 引起的痛觉过敏。这些发现表明，dCA1→ACC 神经元通路参与驱动小鼠在乙醇依赖之前的 EW 诱导的痛觉过敏。
