Psychophysics/hyperalgesia: The A118G single nucleotide polymorphism of the mu-opioid receptor gene (OPRM1) is associated with pressure pain sensitivity in humans

Abstract

Responses to painful stimuli are characterized by tremendous inter-individual variability, and genetic factors likely account for some proportion of this variability. However, few studies have identified genetic contributions to experimental pain perception in humans. This experiment investigated whether the A118G single nucleotide polymorphism (SNP) of the mu-opioid receptor gene (OPRM1) was associated with responses to three different experimental pain modalities in a sample of 157 healthy volunteers (88 female, 69 male). The following psychophysical pain measures were obtained in all subjects: heat pain threshold and tolerance, temporal summation of thermal pain, pressure pain threshold at three sites (trapezius, ulna, and masseter), and ischemic pain threshold and tolerance. Using DNA extracted from whole blood, a 302 base pair fragment of the OPRM1 gene was PCR amplified and sequenced using PCR primers. Genotyping of OPRM1 revealed that the rarer allele at A118G occurred in 20 females (22%) and 11 males (16%). Statistical analyses indicated no significant genotype group differences in thermal or ischemic pain responses; however, subjects with the rare allele had significantly higher pressure pain thresholds than those homozygous for the common allele. While no interaction with sex emerged, the effect sizes (Cohen's D) for the genotype difference ranged from .46 to .84 for males and ..13 to .42 for females, suggesting a stronger association among males. Independent of genotype, sex differences also emerged for heat pain tolerance and pressure pain threshold. These data indicate an association of a common SNP of OPRM1 with mechanical pain responses, especially among men, providing the first evidence in humans that this previously identified candidate gene may indeed be association with pain sensitivity. Potential mechanisms underlying these results are discussed.