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 the effects of anger-out on post-operative analgesic requirements were moderated by the A118G single nucleotide polymorphism of the mu opioid receptor gene. This study further explored these potential genotype X phenotype 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-out X A118G 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-out X A118G interactions were not, suggesting unique effects of expressive anger regulation. Results support opioid-related genotype X phenotype interactions involving trait anger-out.

Pain-related effects of trait anger expression: Neural substrates and the role of endogenous opioid mechanisms

“…Results of Bruehl et al (2008b) suggest the former effect is more pronounced in those highest in anger-out, whereas those of Bruehl et al (2006b) suggest the latter effect is also more pronounced in those higher in anger-out. Thus, both studies indicate that previously reported pain-related effects of the A118G SNP are greatest in individuals highest in trait anger-out.…”

“…Possible mediation or moderation of the effects of trait anger-out on experimental acute pain responsiveness by the A118G SNP has also been examined (Bruehl et al, 2008b). Genetic samples and a measure of trait anger-out were obtained in 87 subjects who participated in controlled laboratory acute pain tasks (ischemic, finger pressure, thermal).…”

Variation in the μ-opioid receptor gene (OPRM1) is associated with dispositional and neural sensitivity to social rejection

“…It also appears that the greater experience of pain among G allele carriers elicits the increased morphine administration (34,41,42). These data, as well as evidence from experimental pain studies (43)(44)(45), indicate that the A118G polymorphism is involved in physical pain sensitivity and thus may be a good candidate for being involved in social pain sensitivity as well.…”

Impact of Prospectively Determined A118G Polymorphism on Treatment Response to Injectable Naltrexone Among Methamphetamine-Dependent Patients

“…Following published methods (Gelernter, Kranzler et al 1999; Bruehl, Chung et al 2008), PCR primers were designed (5’-ccg tca gta cca tgg aca gca gcg gtg-3’ and 5’-gtt cgg acc gca tgg gtc gga cag at-3’) that incorporate mismatched bases to produce an artificial restriction site in a 154-bp PCR product. Amplification consisted of 30 cycles of 95°C for 30 s, 69.7°C for 30 s, and 72°C for 30 s, with a 5 minute final extension at 72°C.…”