Matic Maja, van den Bosch Gerbrich E, de Wildt Saskia N, Tibboel Dick, van Schaik Ron H N
Department of Clinical Chemistry, Erasmus MC-University Medical Centre Rotterdam, Rotterdam, the Netherlands.
Intensive Care and Department of Paediatric Surgery, Erasmus MC-University Medical Centre Rotterdam, Sophia Children's Hospital, Rotterdam, the Netherlands.
Pain. 2016 Nov;157(11):2476-2482. doi: 10.1097/j.pain.0000000000000664.
Pain sensitivity is an inherited factor that varies strongly between individuals. We investigated whether genetic polymorphisms in the candidate genes COMT, OPRM1, OPRD1, TAOK3, TRPA1, TRPV1, and SCN9A are contributing to experimental pain variability between children. Our study included 136 children and adolescents (8-18 years). Cold and heat pain thresholds were determined with a Thermal Sensory Analyzer. Women and young children were significantly more sensitive to pain (P < 0.05). After correction for age, gender, reaction time, and correction for multiple testing, OPRM1 118A>G G-allele carriers (AG and GG) rated the hot stimulus as significantly less painful than did OPRM1 118A>G AA genotyped individuals (2[1-5] vs 7 [3-9], respectively; P = 0.00005). Additionally, OPRM1 118G allele carriers reached more frequently the minimum temperature limit (44% vs 17%, respectively; P = 0.003) and maximum temperature limit (52% vs 24%, respectively; P = 0.0052), indicative for lower pain sensitivity. The combined genotype, based on expected pain sensitivity, OPRM1 118AA/COMT 472 GA or AA genotyped children, was associated with lower pain thresholds (ie, higher pain sensitivity) than were the OPRM1 118GA or GG/COMT 472GG genotyped children. This is the first study reporting on genetic variants and experimental thermal pain in children and adolescents. OPRM1 rs1799971 and the combined OPRM1/COMT genotype could serve as biomarkers for pain sensitivity.
疼痛敏感性是一个在个体间差异很大的遗传因素。我们研究了候选基因COMT、OPRM1、OPRD1、TAOK3、TRPA1、TRPV1和SCN9A中的基因多态性是否导致儿童实验性疼痛的变异性。我们的研究纳入了136名儿童和青少年(8 - 18岁)。使用热感觉分析仪测定冷痛和热痛阈值。女性和年幼儿童对疼痛更敏感(P < 0.05)。在校正年龄、性别、反应时间以及多重检验校正后,OPRM1 118A>G G等位基因携带者(AG和GG)对热刺激的疼痛评分明显低于OPRM1 118A>G AA基因型个体(分别为2[1 - 5] vs 7[3 - 9];P = 0.00005)。此外,OPRM1 118G等位基因携带者更频繁地达到最低温度极限(分别为44% vs 17%;P = 0.003)和最高温度极限(分别为52% vs 24%;P = 0.0052),表明疼痛敏感性较低。基于预期疼痛敏感性的联合基因型,即OPRM1 118AA/COMT 472 GA或AA基因型的儿童,与OPRM1 118GA或GG/COMT 472GG基因型的儿童相比,疼痛阈值更低(即疼痛敏感性更高)。这是第一项报道儿童和青少年基因变异与实验性热痛关系的研究。OPRM1 rs1799971以及联合的OPRM1/COMT基因型可作为疼痛敏感性的生物标志物。