Aguilar Jhoan, De Carvalho Luana Martins, Chen Hu, Condon Ryan, Lasek Amy W, Pradhan Amynah A
Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA.
Alcohol Clin Exp Res (Hoboken). 2024 Mar;48(3):478-487. doi: 10.1111/acer.15273. Epub 2024 Feb 20.
Alcohol withdrawal-induced hyperalgesia (AWH) is characterized as an increased pain sensitivity observed after cessation of chronic alcohol use. Alcohol withdrawal-induced hyperalgesia can contribute to the negative affective state associated with abstinence and can increase susceptibility to relapse. We aimed to characterize pain sensitivity in mice during withdrawal from two different models of alcohol exposure: chronic drinking in the dark (DID) and the Lieber-DeCarli liquid diet. We also investigated whether treatment with a histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), could ameliorate AWH in mice treated with the Lieber-DeCarli diet.
Male and female C57BL/6J mice were used for these studies. In the DID model, mice received bottles of 20% ethanol or water during the dark cycle for 4 h per day on four consecutive days per week for 6 weeks. Peripheral mechanical sensitivity was measured weekly the morning of Day 5 using von Frey filaments. In the Lieber-DeCarli model, mice received ethanol (5% v/v) or control liquid diet for 10 days, along with a single binge ethanol gavage (5 g/kg) or control gavage, respectively, on Day 10. Peripheral mechanical sensitivity was measured during the liquid diet administration and at 24 and 72 h into ethanol withdrawal. An independent group of mice that received the Lieber-DeCarli diet were administered SAHA (50 mg/kg, i.p.) during withdrawal.
Male mice exhibited mechanical hypersensitivity after consuming ethanol for 5 weeks in the DID procedure. In the Lieber-DeCarli model, ethanol withdrawal led to hyperalgesia in both sexes. Suberoylanilide hydroxamic acid treatment during withdrawal from the ethanol liquid diet alleviated AWH.
These results demonstrate AWH in mice after chronic binge drinking in males and after Lieber-DeCarli liquid diet administration in both sexes. Like previous findings in rats, HDAC inhibition reduced AWH in mice, suggesting that epigenetic mechanisms are involved in AWH.
酒精戒断所致痛觉过敏（AWH）的特征是在长期饮酒停止后观察到疼痛敏感性增加。酒精戒断所致痛觉过敏可导致与戒酒相关的负面情绪状态，并增加复发易感性。我们旨在描述两种不同酒精暴露模型戒断期间小鼠的疼痛敏感性：黑暗中慢性饮酒（DID）和Lieber-DeCarli液体饮食。我们还研究了用组蛋白脱乙酰酶（HDAC）抑制剂辛二酰苯胺异羟肟酸（SAHA）治疗是否能改善接受Lieber-DeCarli饮食的小鼠的AWH。
使用雄性和雌性C57BL/6J小鼠进行这些研究。在DID模型中，小鼠在每周连续4天的黑暗周期中每天接受装有20%乙醇或水的瓶子，持续6周，每天4小时。每周第5天上午使用von Frey细丝测量外周机械敏感性。在Lieber-DeCarli模型中，小鼠分别接受乙醇（5% v/v）或对照液体饮食10天，并在第10天分别接受一次大剂量乙醇灌胃（5 g/kg）或对照灌胃。在给予液体饮食期间以及乙醇戒断24小时和72小时时测量外周机械敏感性。另一组接受Lieber-DeCarli饮食的小鼠在戒断期间给予SAHA（50 mg/kg，腹腔注射）。
在DID程序中，雄性小鼠在饮用乙醇5周后表现出机械性超敏反应。在Lieber-DeCarli模型中，乙醇戒断导致两性均出现痛觉过敏。从乙醇液体饮食戒断期间用辛二酰苯胺异羟肟酸治疗可减轻AWH。
这些结果表明，雄性小鼠长期暴饮后以及两性接受Lieber-DeCarli液体饮食后均出现AWH。与先前在大鼠中的发现一样，HDAC抑制可减轻小鼠的AWH，表明表观遗传机制参与了AWH。
