Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing Engineering Research Center for Laboratory Animal Models of Human Critical Diseases, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China.
Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
Animal Model Exp Med. 2022 Sep;5(3):288-296. doi: 10.1002/ame2.12234. Epub 2022 Jun 3.
Morphine is a widely used analgesic, but its use in clinical precision medicine is limited by the variance in response among individuals. Although previous studies have shown that individual differences in morphine can be explained in terms of pharmacodynamics and pharmacokinetics, genetic polymorphisms also play an important role. However, the genetic basis of different sensitivity and tolerance susceptibility to morphine remains ambiguous. Using 15 strains of inbred Genetic Diversity (GD) mice, a new resource with wide genetic and phenotypic variation, we demonstrated great variance in sensitivity to morphine analgesia and susceptibility to morphine tolerance between different GD strains. Among-individual variance in response to morphine analgesia in the population can be modeled in GD mice. Two loci respectively may be associated with the among-individual variance in morphine sensitivity and tolerance, confirming the role of genetic factors in among-individual different responses to morphine. These results indicate that GD mice may be a potential tool for the identification of new biomarkers to improve the clinical administration of morphine.
吗啡是一种广泛使用的镇痛药，但由于个体间反应的差异，其在临床精准医学中的应用受到限制。尽管先前的研究表明，吗啡个体差异可以用药效学和药代动力学来解释，但遗传多态性也起着重要作用。然而，不同个体对吗啡的敏感性和耐受性差异的遗传基础仍不清楚。本研究使用 15 个近交遗传多样性（GD）小鼠品系，这是一种具有广泛遗传和表型变异的新资源，证明了不同 GD 品系之间对吗啡镇痛的敏感性和对吗啡耐受的易感性存在巨大差异。在 GD 小鼠中可以对吗啡镇痛反应的个体间差异进行建模。两个基因座可能分别与吗啡敏感性和耐受性的个体间差异相关，证实了遗传因素在个体对吗啡反应的个体间差异中的作用。这些结果表明，GD 小鼠可能是一种潜在的工具，用于鉴定新的生物标志物，以改善吗啡的临床应用。
