The mu opioid receptor A118G gene polymorphism moderates effects of trait anger-out on acute pain sensitivity

Abstract

Both trait anger-in (managing anger through suppression) and anger-out (managing anger through direct expression) are related to pain responsiveness, but only anger-out effects involve opioid mechanisms. Preliminary work suggested that the effects of anger-out on postoperative analgesic requirements were moderated by the A118G single nucleotide polymorphism of the mu opioid receptor gene. This study further explored these potential genotypexphenotype interactions as they impact acute pain sensitivity. Genetic samples and measures of anger-in and anger-out were obtained in 87 subjects (from three studies) who participated in controlled laboratory acute pain tasks (ischemic, finger pressure, thermal). McGill Pain Questionnaire (MPQ) Sensory and Affective ratings for each pain task were standardized within studies, aggregated across pain tasks, and combined for analyses. Significant anger-outxA118G interactions were observed (p's<.05). Simple effects tests for both pain measures revealed that whereas anger-out was nonsignificantly hyperalgesic in subjects homozygous for the wild-type allele, anger-out was significantly hypoalgesic in those with the variant G allele (p's<.05). For the MPQ-Affective measure, this interaction arose both from low pain sensitivity in high anger-out subjects with the G allele and heightened pain sensitivity in low anger-out subjects with the G allele relative to responses in homozygous wild-type subjects. No genetic moderation was observed for anger-in, although significant main effects on MPQ-Affective ratings were noted (p<.005). Anger-in main effects were due to overlap with negative affect, but anger-outxA118G interactions were not, suggesting unique effects of expressive anger regulation. Results support opioid-related genotypexphenotype interactions involving trait anger-out.

Figure 1

Scatterplot of MPQ-Sensory pain ratings by anger-out score as a function of A118G SNP status.

Figure 2

Effects of anger-out on MPQ-Sensory standardized pain ratings in subjects with the wild-type (A/A) and variant G allele. Anger-out values plotted are hypothetical values representing one standard deviation (SD) below and above the sample mean. Greater positive MPQ-Sensory scores indicate greater pain intensity. AOS = Anger-Out Scale.

Figure 3

Effects of anger-out on MPQ-Affective standardized pain ratings in subjects with the wild-type (A/A) and variant G allele.