Qadri Yawar J, Bortsov Andrey V, Orrey Danielle C, Swor Robert A, Peak David A, Jones Jeffrey S, Rathlev Niels K, Lee David C, Domeier Robert M, Hendry Phyllis L, Mclean Samuel A
Department of Anesthesiology, University of North Carolina, Chapel Hill, NC.
Department of Emergency Medicine, William Beaumont Hospital, Royal Oak.
Clin J Pain. 2015 Sep;31(9):768-775. doi: 10.1097/AJP.0000000000000167.
Dopaminergic signaling is implicated in nociceptive pathways. These effects are mediated largely through dopamine receptors and modulated in part by dopamine transporters. This study tested 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.
European Americans presenting to the emergency department after motor vehicle collision were recruited. Overall pain intensity in emergency department was assessed using a 0 to 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.
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% confidence interval [CI], 5.1-5.5) than those with A/G (5.9; 95% CI, 5.6-6.1) or G/G (5.7; 95% CI, 5.2-6.2) genotypes (P=0.0027). Secondary analyses revealed an interaction between sex and DRD2 SNPs rs4586205 and rs4648318 on pain scores: females with 2 minor alleles had increased pain intensity, whereas males with 2 minor alleles had less pain than individuals with a major allele (interaction P=0.0019).
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 posttraumatic pain as part of a multimodal opioid-sparing analgesic regimen.
多巴胺能信号传导与伤害感受通路有关。这些作用主要通过多巴胺受体介导，部分受多巴胺转运体调节。本研究检验了以下假设：编码多巴胺受体2（DRD2）和多巴胺活性转运体（SLC6A3）的基因中的遗传变异会影响机动车碰撞后的急性疼痛严重程度。
招募机动车碰撞后到急诊科就诊的欧裔美国人。使用0至10的数字评分量表评估急诊科的总体疼痛强度。从血样中提取DNA，并对DRD2和SLC6A3基因中的单核苷酸多态性（SNP）进行基因分型。
共有948名患者完成评估。在进行多重比较校正后，DRD2基因的SNP rs6276与疼痛评分显著相关，A/A基因型个体报告的平均疼痛评分（5.3；95%置信区间[CI]，5.1 - 5.5）低于A/G基因型个体（5.9；95%CI，5.6 - 6.1）或G/G基因型个体（5.7；95%CI，5.2 - 6.2）（P = 0.0027）。二次分析显示，性别与DRD2基因SNP rs4586205和rs4648318在疼痛评分上存在相互作用：具有2个次要等位基因的女性疼痛强度增加，而具有2个次要等位基因的男性比具有主要等位基因的个体疼痛较轻（相互作用P = 0.0019）。
DRD2基因的遗传变异与创伤应激事件后的急性疼痛有关。这些结果表明，多巴胺能药物作为多模式阿片类药物节省镇痛方案的一部分，可能对治疗急性创伤后疼痛的个体有用。
