Association between human opioid receptor genes polymorphisms and pressure pain sensitivity in females*

Abstract

This study examined the association between pressure pain sensitivity and various single nucleotide polymorphisms (SNPs) of human l-, j-, and d-opioid receptor (i.e. OPRM1, OPRK1, and OPRD1) genes in 72 healthy adult Taiwanese women of Han Chinese race. Pressure pain threshold and tolerance were measured by an algometer and polymorphisms of the opioid receptor genes determined from blood samples. Our data revealed that pressure pain threshold, but not tolerance, in subjects with the minor allele (termed 'GA') genotype of the IVS2+31G>A polymorphism of the OPRM1 gene was significantly higher than those with major allele (termed 'GG') genotype. Neither pressure pain threshold nor tolerance between major and minor alleles of other SNPs of the OPRM1, OPRK1, and OPRD1 genes were significantly different. These data suggest an association between the IVS2+31G>A SNP of the OPRM1 gene and pressure pain sensitivity in healthy adult females. We have previously shown that pre-operative pressure pain sensitivity, especially pressure pain tolerance, predicts postoperative pain and analgesic consumption in female patients [1]. However, the mechanisms that underlie the substantial inter-individual variability in pressure pain sensitivity in females remain to be elucidated.The human l-opioid receptor mediates the analgesic effects of endogenous opioid peptides and exogenous opioid agents [2]. The function of the l-receptor is under the influence of single nucleotide polymorphisms (SNPs) of the human l-opioid receptor (OPRM1) gene [3]. With an incidence of 10-15%, the 118A>G SNP is one of the most widely studied SNPs of the OPRM1 gene [4]. In the terminology, '118' refers to the position of this SNP in the genome (i.e. position 118 in the exon) and 'A>G' represents a possible substitution of the nucleotide adenine, A, by guanine, G [4]. The genotype of individuals in relation to this SNP can therefore be homozygous GG, or -where a substitution occurshomozygous AA, or heterozygous AG. As the incidence of AA is significantly higher than that of GG, the genotype AA is referred to as the 'major homozygous genotype' and the genotype GG is referred to as the 'minor homozygous genotype' of this SNP [4].Fillingim et al. reported that the 118A>G SNP of the OPRM1 gene was associated with pressure pain sensitivity in healthy adults: individuals with heterozygous (AG) and minor homozygous (GG) genotypes of this SNP were found to have higher pressure pain threshold than individuals with major homozygous (AA) genotype [5]. However, when data from men and women were analysed separately this association of genotype with response was only significant in men [5]. Since substantial inter-individual variability in pressure pain sensitivity also exists in females, these data suggest that the 118A>G SNP of the OPRM1 gene may not be the mechanism that

‘Hardy’s Law’ and genomics in Anaesthesia

“…Hardy's little letter [4] offers insight into the data presented by Huang et al [1]. Such studies will soon -properlybecome commonplace in our clinical anaesthetic literature.…”

“…The human population is assumed both relatively large and stable, but allele frequencies may differ across ethnic groups (a point made by Huang et al [1]) [7]. Hardy's Law also assumes near-random mating of roughly equal males and females within a population, so enforced mating of animals or selectively altering the male:female ratio will cause allele proportions to deviate from those predicted by Hardy's Law.…”

How Much Oxycodone Is Needed for Adequate Analgesia After Breast Cancer Surgery: Effect of the OPRM1 118A>G Polymorphism

“…24 In our study there was no association between either experimental heat or cold pain sensitivity and the 118A>G polymorphism in agreement with Huang and co-workers. 12 It is not surprising that the fairly low intensity stimulation with 48°C for 5 s did not show any association with the polymorphism. However, one would have expected an association in the cold pain test, which is very unpleasant and could activate stress-induced analgesia which is at least partly mediated by the endogenous opioid system.…”

Extensive Changes in the Expression of the Opioid Genes between Humans and Chimpanzees

“…Opioid gene signaling is a critical link in a number of human behavioral responses [reviewed in Sonetti et al, 2005;Bodnar, 2009;Stein and Zollner, 2009], as well as in many human disease susceptibilities [Kreek, 1996a;Ogden et al, 2004;Kreek et al, 2005;Drakenberg et al, 2006;Kennedy et al, 2006;Xuei et al, 2006Xuei et al, , 2007Huang et al, 2008;Nikoshkov et al, 2008;Bodnar, 2009]. Several studies have presented evidence of functional changes that have occurred in the coding sequences of these genes, both across vertebrate evolution [Dores et al, 2002;Stevens et al, 2007;Dreborg et al, 2008] and within human populations (e.g.…”

“…The primary and secondary binding affinities of these ligands and receptors are illustrated in figure 1 [Chen et al, 1993a;Meng et al, 1996;Gong et al, 1998;Zaveri et al, 2001;Snook et al, 2008;Liu et al, 2009]. Most investigations surrounding this gene family have focused on the role its members play in pain and nocicep-155 tion [reviewed in Stein and Zollner, 2009], stress response [Sonetti et al, 2005], behavior [reviewed in Bodnar, 2009], substance abuse [Kreek, 1996;Kreek et al, 2005;Drakenberg et al, 2006;Xuei et al, 2006Xuei et al, , 2007Huang et al, 2008;Nikoshkov et al, 2008], and some psychiatric affective disorders [reviewed in Ogden et al, 2004;Kennedy et al, 2006;Bodnar, 2009].…”