Fu Rao, Gregor Danielle, Peng Zengliu, Li Jing, Bekker Alex, Ye Jianghong
Department of Anesthesiology, Pharmacology and Physiology, Rutgers, The State University of New Jersey, New Jersey Medical School Newark, NJ, USA.
Int J Physiol Pathophysiol Pharmacol. 2015 Dec 13;7(3):136-44. eCollection 2015.
The mechanisms of hyperalgesia in alcoholics are not completely clear, and the development of animal models would therefore be necessary in investigating the underlying changes. Several studies including our own have demonstrated that the intermittent access to 20% ethanol two-bottle choice procedure (IA2BC) promotes escalation of drinking, and induces physical dependence in the Sprague-Dawley (SD) rat, one of the strains most commonly used in preclinical alcohol research. In this study, we investigated whether the IA2BC procedure could produce hyperalgesia in SD rats. We show here that, the SD rats in the IA2BC procedure significantly escalated their drinking within 8 weeks, which is consistent with other studies. Starting from 8 weeks of repeated chronic drinking, the mechanical and thermal sensitivity was significantly increased. During withdrawal, there were noticeable physical dependence signs, including tail stiffness and lower limb flexion, which started at 4 hours and lasted for more than 3 days after ethanol removal. Importantly, during withdrawal, the mechanical and thermal sensitivity was further increased, which started at 12 hours and lasted for more than seven days after ethanol removal. These results suggest that utilizing the SD rat under the IA2BC procedure could be a useful animal model with heuristic value for exploring the mechanisms underlying hyperalgesia induced by chronic alcohol abuse.
酗酒者痛觉过敏的机制尚不完全清楚,因此有必要建立动物模型来研究其潜在变化。包括我们自己的研究在内的多项研究表明,间歇性接触20%乙醇双瓶选择程序(IA2BC)会促使饮酒量增加,并使Sprague-Dawley(SD)大鼠产生身体依赖性,SD大鼠是临床前酒精研究中最常用的品系之一。在本研究中,我们调查了IA2BC程序是否会在SD大鼠中产生痛觉过敏。我们在此表明,IA2BC程序中的SD大鼠在8周内饮酒量显著增加,这与其他研究一致。从8周的反复慢性饮酒开始,机械敏感性和热敏感性显著增加。在戒断期间,出现了明显的身体依赖迹象,包括尾巴僵硬和下肢屈曲,在乙醇撤除后4小时开始出现,并持续超过3天。重要的是,在戒断期间,机械敏感性和热敏感性进一步增加,在乙醇撤除后12小时开始出现,并持续超过7天。这些结果表明,在IA2BC程序下使用SD大鼠可能是一种有用的动物模型,对探索慢性酒精滥用引起的痛觉过敏的潜在机制具有启发价值。