Rogers Walker D, White Alyssa, Damaj M Imad, Miles Michael F
Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia, United States.
Alcohol Research Center, Virginia Commonwealth University, Richmond, Virginia, United States.
bioRxiv. 2024 Jun 17:2024.06.17.599372. doi: 10.1101/2024.06.17.599372.
Alcohol consumption produces acute analgesic effects, and people experiencing pain conditions may drink alcohol to alleviate discomfort. However, tolerance to the analgesic properties of alcohol could prompt escalating consumption and dependence. Both nociception and alcohol-induced analgesia are under significant genetic control. Understanding the genetic architecture of these processes could inform better treatment options for people with pain conditions. This study aims to identify quantitative trait loci (QTL) driving variation in ethanol-induced analgesia across BXD recombinant inbred mouse lines. Male and female mice from 62 BXD strains received ethanol or saline oral gavage for five days and were tested for hot plate (HP) latency at baseline, Day 1, and Day 5. QTL mapping of HP phenotypes identified a significant provisional QTL on chromosome 17 for Day 1 HP latency in mice receiving ethanol. An additional highly suggestive QTL was present on chromosome 9 for the difference in pre- and post-ethanol thermal nociception. Candidate genes within QTL support intervals were provisionally identified using HP phenotypic correlations to transcriptomic database, expression QTL analysis, and other bioinformatics inquiries. The combined behavioral and bioinformatic analyses yielded strong ethanol analgesia candidate genes, specifically . Thus, the results of this genetic study of ethanol-induced analgesia in BXD mouse strains may contribute significantly to our understanding of the molecular basis for individual variation in the analgesic response to acute ethanol.
饮酒会产生急性镇痛作用，处于疼痛状态的人可能会饮酒以减轻不适。然而，对酒精镇痛特性的耐受性可能会促使饮酒量增加和产生依赖。伤害感受和酒精诱导的镇痛都受到显著的基因控制。了解这些过程的遗传结构可以为疼痛患者提供更好的治疗选择。本研究旨在确定驱动BXD重组近交系小鼠乙醇诱导镇痛差异的数量性状基因座（QTL）。来自62个BXD品系的雄性和雌性小鼠接受乙醇或生理盐水灌胃5天，并在基线、第1天和第5天测试热板（HP）潜伏期。对HP表型进行QTL定位，发现在接受乙醇的小鼠中，第1天HP潜伏期在17号染色体上有一个显著的临时QTL。在9号染色体上存在另一个高度提示性的QTL用于乙醇前后热伤害感受的差异。利用HP表型与转录组数据库的相关性、表达QTL分析和其他生物信息学查询，初步确定了QTL支持区间内的候选基因。行为和生物信息学分析相结合产生了强有力的乙醇镇痛候选基因，特别是。因此，这项关于BXD小鼠品系乙醇诱导镇痛的遗传学研究结果可能会极大地有助于我们理解急性乙醇镇痛反应个体差异的分子基础。
