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Genetic variants associated with thermal pain sensitivity in a paediatric population

Matic, Maja; van den Bosch, Gerbrich E.; de Wildt, Saskia N.; Tibboel, Dick; van Schaik, Ron H.N.

doi: 10.1097/j.pain.0000000000000664
Research Paper

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.

Supplemental Digital Content is Available in the Text.Children with OPRM1 118G allele and the combined genotype OPRM1 118G allele carriers with COMT 472GG are less sensitive to thermal pain.

aDepartment of Clinical Chemistry, Erasmus MC—University Medical Centre Rotterdam, Rotterdam, the Netherlands

bIntensive Care and Department of Paediatric Surgery, Erasmus MC—University Medical Centre Rotterdam, Sophia Children's Hospital, Rotterdam, the Netherlands

cDepartment of Pharmacology and Toxicology, Radboud University Medical Centre, Nijmegen, the Netherlands

Corresponding author. Address: Erasmus University Hospital Rotterdam—Sophia Children's Hospital, Room Na—415, Wytemaweg 80, 3015 CN Rotterdam, the Netherlands. Tel.: +31 (0) 10 70 43396. E-mail address: (M. Matic).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Received February 29, 2016

Received in revised form June 08, 2016

Accepted July 07, 2016

© 2016 International Association for the Study of Pain
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