Genetic and epigenetic mechanisms influencing acute to chronic postsurgical pain transitions in pediatrics: Preclinical to clinical evidence.
Genetic and epigenetic mechanisms influencing acute to chronic postsurgical pain transitions in pediatrics: Preclinical to clinical evidence.
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DOI：
10.1080/24740527.2021.2021799
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发表时间：
2022
影响因子：
2.4
通讯作者：
Chidambaran, Vidya
中科院分区：
文献类型：
--
作者：
Dourson, Adam J.;Willits, Adam;Raut, Namrata G. R.;Kader, Leena;Young, Erin;Jankowski, Michael P.;Chidambaran, Vidya
关键词：
儿童慢性手术后疼痛(CPSP)仍然是一个重要的问题，没有有效的预防或治疗策略。最近，已经提出了解释心理因素以外的额外个体间风险的基因组基础。我们对目前有关儿童CPSP的遗传和表观遗传机制的临床前和临床证据进行了全面的综述。叙事性回顾。动物模型与解开基因组机制的翻译研究相关。例如，Cacng2、p2rx7和BDNF突变小鼠对损伤表现出机械超敏反应，相同基因的变异与人类CPSP易感性有关；类似地，差异DNA甲基化(H1SP)和miRNAs(miR-96/7a)也显示出翻译含义。动物研究还表明，神经元和免疫细胞之间的串扰可能参与了在新生儿中观察到的伤害性启动。在儿童中，富含GABA能、多巴胺能和免疫途径的调节基因组区域的不同DNA甲基化，以及用于增强CPSP预测的多基因风险分数已被描述。儿童CPSP的全基因组研究很少，但成人基因关联研究确定的通路指出了潜在的共同机制。儿科CPSP的床边基因组学研究目前是有限的。反向翻译方法，使用其他组学，以及在大规模生物库中纳入儿科/CPSP内表型可能是潜在的解决方案。术后发育易损性时间和纵向基因组变化值得进一步研究。基于基因编辑和表观遗传学编程的有前景的精确疼痛管理策略的出现强调了在儿科CPSP相关基因组学方面进一步研究的必要性。
Chronic postsurgical pain (CPSP) in children remains an important problem with no effective preventive or therapeutic strategies. Recently, genomic underpinnings explaining additional interindividual risk beyond psychological factors have been proposed. We present a comprehensive review of current preclinical and clinical evidence for genetic and epigenetic mechanisms relevant to pediatric CPSP. Narrative review. Animal models are relevant to translational research for unraveling genomic mechanisms. For example, Cacng2, p2rx7, and bdnf mutant mice show altered mechanical hypersensitivity to injury, and variants of the same genes have been associated with CPSP susceptibility in humans; similarly, differential DNA methylation (H1SP) and miRNAs (miR-96/7a) have shown translational implications. Animal studies also suggest that crosstalk between neurons and immune cells may be involved in nociceptive priming observed in neonates. In children, differential DNA methylation in regulatory genomic regions enriching GABAergic, dopaminergic, and immune pathways, as well as polygenic risk scores for enhanced prediction of CPSP, have been described. Genome-wide studies in pediatric CPSP are scarce, but pathways identified by adult gene association studies point to potential common mechanisms. Bench-to-bedside genomics research in pediatric CPSP is currently limited. Reverse translational approaches, use of other -omics, and inclusion of pediatric/CPSP endophenotypes in large-scale biobanks may be potential solutions. Time of developmental vulnerability and longitudinal genomic changes after surgery warrant further investigation. Emergence of promising precision pain management strategies based on gene editing and epigenetic programing emphasize need for further research in pediatric CPSP-related genomics.
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影响因子：
3.7
作者：
Boks MP;Derks EM;Weisenberger DJ;Strengman E;Janson E;Sommer IE;Kahn RS;Ophoff RA
通讯作者：
Ophoff RA
影响因子：
5.7
作者：
Bermick JR;Lambrecht NJ;denDekker AD;Kunkel SL;Lukacs NW;Hogaboam CM;Schaller MA
通讯作者：
Schaller MA
DOI：
10.1016/j.trsl.2014.05.012
发表时间：
2015-01
期刊：
Translational research : the journal of laboratory and clinical medicine
影响因子：
--
作者：
Bai G;Ren K;Dubner R
通讯作者：
Dubner R
影响因子：
5
作者：
Bie, Bihua;Brown, David L.;Naguib, Mohamed
通讯作者：
Naguib, Mohamed
影响因子：
25.8
作者：
Andersen, Allan M.;Pietrzak, Robert H.;Han, Shizhong
通讯作者：
Han, Shizhong