title: Genetic variants associated with thermal pain sensitivity in a paediatric population.
abstract: 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.
authors.affiliation: 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.
authors.forename: Maja
authors.initials: M
authors.lastname: Matic
authors.affiliation: Intensive Care and Department of Paediatric Surgery, Erasmus MC-University Medical Centre Rotterdam, Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Gerbrich E
authors.initials: GE
authors.lastname: van den Bosch
authors.affiliation: Intensive Care and Department of Paediatric Surgery, Erasmus MC-University Medical Centre Rotterdam, Sophia Children's Hospital, Rotterdam, the Netherlands.|Department of Pharmacology and Toxicology, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: Saskia N
authors.initials: SN
authors.lastname: de Wildt
authors.affiliation: Intensive Care and Department of Paediatric Surgery, Erasmus MC-University Medical Centre Rotterdam, Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.affiliation: Department of Clinical Chemistry, Erasmus MC-University Medical Centre Rotterdam, Rotterdam, the Netherlands.
authors.forename: Ron H N
authors.initials: RHN
authors.lastname: van Schaik
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D006930:Hyperalgesia / Q000235:genetics*; D008297:Male; D017711:Nonlinear Dynamics; D017288:Pain Threshold / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D012737:Sex Factors; D013696:Temperature
chemical_list: C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase