GENETIC VARIANTS AND PAIN RESPONSE IN CHILDREN

Milena Flória Santos

Debra L. Schutte

Ann Marie Mccarthy

Chamaine Kleiber

The integration of molecular genetics approaches into the study of complex health phenomena is an increasingly important and available strategy for researchers across the health science disciplines. These approaches can be applied to study pain sensation and response to painful stimuli. Children demonstrate variability in response to painful medical procedures, and evidence suggests that these differences may be related, in part, to genetic variation. The identification of genes that influence children's pain response is needed in order to develop and prescribe the most appropriate interventions. The purpose of this study is to examine the contribution of sequence variations within candidate genes for pain to variable pain response in children undergoing an IV catheter insertion. Three hundred eighty seven children (age 4-10 years), scheduled for an IV insertion prior to a diagnostic procedure, and their parents were recruited from three different outpatient settings. All subjects received a topical analgesic before the IV insertion. Cheek swabs for DNA extraction and subsequent genotyping were collected from the children and available biological parents. Taqman quantitative PCR assay system was used to detect single nucleotide polymorphisms within 7 candidate pain genes, hypothesized to play a role in pain perception and transmission pathways. Measures of child response to the IV insertion included: child self-report measure of pain (OUCHER Scale), behavioral measure of child distress (OSBD-R), and parent report of child distress. An Oucher score of 0-3 was defined as low pain a score of 4-10 was defined as high pain. Comparisons between pain phenotype and predictor variables were examined with correlation and chi-square. Statistically significant differences were found between the high and low pain groups on age (high pain group, younger age, p=. 0001), child temperament-task orientation (>75th %; higher pain, less orientation, p=0. 020), child temperament-general activity (> 75th %; higher pain, higher activity, p=0. 017). Our analysis indicates that 80% of subjects with at least one copy of the Brain-derived Neurotrophic Growth Factor (BDNF) 198A-allele, and 79% of children with the Endothelin Receptor A (EDNRA) TT genotype are in the high pain response group. Results from this study will contribute to the understanding of the genetic basis of pain and distress and will improve the ability to more effectively develop and prescribe interventions.

Correspondência para: Milena Flória-Santos, e-mail: mfloria-santos@uiowa.edu