Genetic Polymorphisms in the Dopamine Receptor 2 Predict Acute Pain Severity After Motor Vehicle Collision

Abstract

Objectives: Dopaminergic signaling is implicated in nociceptive pathways. These effects are mediated largely through dopamine receptors and modulated in part by dopamine transporters. This study tests the hypothesis that genetic variants in the genes encoding dopamine receptor 2 (DRD2) and the dopamine active transporter (SLC6A3) influence acute pain severity after motor vehicle collision (MVC). Methods: European Americans presenting to the emergency department (ED) after MVC were recruited. Overall pain intensity in ED was assessed using a 0-10 numeric rating scale. DNA was extracted from blood samples and genotyping of single nucleotide polymorphisms (SNPs) in the DRD2 and SLC6A3 gene was performed. Results: A total of 948 patients completed evaluation. After correction for multiple comparisons, SNP rs6276 at DRD2 showed significant association with pain scores, with individuals with the A/A genotype reporting lower mean pain scores (5.3, 95% CI 5.1 to 5.5) than those with A/G (5.9, 95% CI 5.6 to 6.1) or G/G (5.7, 95%CI 5.2 to 6.2) genotypes (p=0.0027). Secondary analyses revealed an interaction between sex and DRD2 SNPs rs4586205 and rs4648318 on pain scores: females with two minor alleles had increased pain intensity, whereas males with two minor alleles had less pain than individuals with a major allele (interaction p=0.0019). Discussion: Genetic variants in DRD2 are associated with acute pain after a traumatic stressful event. These results suggest that dopaminergic agents may be useful for the treatment of individuals with acute post-traumatic pain as part of a multimodal opioid-sparing analgesic regimen.

Association Between Polymorphisms in Dopamine‐Related Genes and Orthopedic Pain Expression in a Chinese Elderly Population

“…In addition, it has been demonstrated that genetic variants of the gene DRD2 are linked to responses to acute painful stimuli after a motor vehicle collision within the middle‐aged population . Patients with the rs6276 A/A genotype express lower pain than do individuals with the A/G or G/G genotype . Overall, these data suggest that genetic variants of SLC6A3 and DRD2 can alter acute pain expression.…”

“…Pain tolerance and expression after identical noxious stimuli vary widely among individuals. Genetic factors may contribute to various responses to painful stimuli . The involvement of monoamine neurotransmitters, especially serotonin and norepinephrine, in pain expression is well established, and clinical trials have shown that serotonin norepinephrine reuptake inhibitors are effective against neuropathic pain .…”

“…Evidence from genetic research into the effects of dopamine‐related gene variations on pain is believed to explain, at least in part, individual differences in pain expression . The catecholamine‐ O ‐methyltransferase ( COMT ) rs4680 Val158Met polymorphism is one of the best‐known single‐nucleotide polymorphisms (SNPs) associated with pain expression .…”

“…For example, in a study on healthy human volunteers, variability within DAT or SLC6A3 was found to predict the severity of experimentally induced pain . In addition, it has been demonstrated that genetic variants of the gene DRD2 are linked to responses to acute painful stimuli after a motor vehicle collision within the middle‐aged population . Patients with the rs6276 A/A genotype express lower pain than do individuals with the A/G or G/G genotype .…”

“…An increasing number of studies are examining the association between genetic polymorphisms and pain expression . Nevertheless, several issues need to be considered.…”