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October 16, 2012
1:00:00 PM - 3:00:00 PM
Room West Salon G
Genetic Polymorphisms in the Dopamine Receptor D2 are Associated With Acute Pain Severity After Motor Vehicle Collision
Yawar J. Qadri, M.D.,Ph.D., Andrey V. Bortsov, M.D.,Ph.D., Robert A. Swor, D.O., David A. Peak, M.D., Jeffrey S. Jones, M.D., Niels K. Rathlev, M.D., David C. Lee, M.D., Robert M. Domeier, M.D., Phyllis L. Hendry, M.D., Samuel A. Mclean, M.D.,M.P.H.
University of North Carolina, Chapel Hill, North Carolina, United States
Background: Dopamine is implicated in nociceptive pathways, both centrally and peripherally. These effects are mediated largely through neuronally expressed dopamine receptors. Of the five dopamine receptors, dopamine receptor 2 (DRD2) has been strongly associated with both acute nociception and psychiatric/neurologic disorders. In this study, we tested the hypothesis that genetic variants in the gene encoding DRD2 are associated with the severity of reported pain after minor trauma exposure.

Methods: European American patients, aged 18-65, who presented to the emergency department (ED) after motor vehicle collisions (MVC) and were discharged home were recruited at the time of ED evaluation. Overall pain intensity in ED was assessed using a 0-10 numeric rating scale. DNA was extracted from blood samples (PAXgene Blood Tube) and targeted genotyping (Sequenom platform) of 12 specific single nucleotide polymorphisms (SNPs) in the DRD2 gene was performed. The associations between SNP genotypes and acute pain intensity were evaluated using ANOVA, with adjustment for study site and appropriate correction for multiple comparisons using a modified Bonferroni correction to maintain α = 0.05.

Results: A total of 10,629 patients were screened, 1416 were eligible, 969 consented to study participation, and 948 completed baseline evaluation. One SNP (rs6279) with a low call rate (89%) and one monoallelic SNP (rs4986918) were excluded from analyses. A dominant genetic model appeared to provide the best fit to the data. After adjustment for multiple comparisons, rs6276 showed a statistically significant association with overall pain intensity in ED. Homozygous patients with the AA genotype at rs6276 (n = 448) reported overall pain intensity of 5.3 ± 0.2 while patients with the AG or GG genotype (n = 496) reported overall pain intensity of 5.8 ± 0.2 (p = .0009).

Conclusion: Individuals presenting to the emergency department after a minor MVC with the rs6276 AA genotype report less pain as compared to the patients with the AG or GG genotype. This SNP is located in the 3’-untranslated region of the DRD2, a region known to be important in the stability of mRNA and mRNA regulation. This genetic variant in the gene encoding DRD2 is associated with pain severity after motor vehicle collisions.

Copyright © 2012 American Society of Anesthesiologists