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Ethnicity interacts with the OPRM1 gene in experimental pain sensitivity.

ABSTRACT: Robust interindividual variation in pain sensitivity has been observed, and recent evidence suggests that some of the variability may be genetically mediated. Our previous data revealed significantly higher pressure pain thresholds among individuals possessing the minor G allele of the A118G SNP of the mu-opioid receptor gene (OPRM1) compared with those with 2 consensus alleles. Moreover, ethnic differences in pain sensitivity have been widely reported. Yet, little is known about the potential interactive associations of ethnicity and genotype with pain perception. This study aimed to identify ethnic differences in OPRM1 allelic associations with experimental pain responses. A total of 247 healthy young adults from three ethnic groups (81 African Americans; 79 non-white Hispanics; and 87 non-Hispanic whites) underwent multiple experimental pain modalities (thermal, pressure, ischemic, cold pressor). Few African Americans (7.4%) expressed the rare allele of OPRM1 compared to non-Hispanic whites and Hispanics (28.7% vs. 27.8%, respectively). Across the entire sample, OPRM1 genotype did not significantly affect pain sensitivity. However, analysis in each ethnic group separately revealed significant genotype effects for most pain modalities among non-Hispanic-whites (P<.05) but not Hispanics or African Americans. The G allele was associated with decreased pain sensitivity among whites only; a trend in the opposite direction emerged in Hispanics. The reasons for this dichotomy are unclear; they may involve ethnic differences in haplotypic structure, or A118G may be a tag-SNP linked to other functional polymorphisms. These findings demonstrate an ethnicity-dependent association of OPRM1 genotype with pain sensitivity. Additional research is warranted to uncover the mechanisms influencing these relationships.

SUBMITTER: Hastie BA

PROVIDER: S-EPMC3683662 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Ethnicity interacts with the OPRM1 gene in experimental pain sensitivity.

Hastie Barbara A BA Riley Joseph L JL Kaplan Lee L Herrera Dyanne G DG Campbell Claudia M CM Virtusio Kathrina K Mogil Jeffrey S JS Wallace Margaret R MR Fillingim Roger B RB

Pain 20120618 8

Robust interindividual variation in pain sensitivity has been observed, and recent evidence suggests that some of the variability may be genetically mediated. Our previous data revealed significantly higher pressure pain thresholds among individuals possessing the minor G allele of the A118G SNP of the mu-opioid receptor gene (OPRM1) compared with those with 2 consensus alleles. Moreover, ethnic differences in pain sensitivity have been widely reported. Yet, little is known about the potential i ...[more]

PMID: 22717102

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Project description:BACKGROUND:Osteoarthritis (OA) of the knee is a common and increasingly prevalent condition that is one of the primary causes of chronic pain. Staying physically active protects against disability from knee OA but is also very challenging. A critical but unexamined question is whether patients at greatest risk for becoming less active are those with a genetic predisposition for greater sensitivity to daily pain. AIMS:We examined day-to-day variability in knee OA pain for patients with different variants of catechol-O-methyltransferase (COMT) and mu-opioid receptor (OPRM1) single nucleotide polymorphisms (SNPs), and whether patients with a specific genotype experience more pain following daily physical activity. We predicted that patients having one or more copies of the Met158 allele of COMT rs4680 (A-A or A-G) and one or more copies of the Asp40 allele of OPRM1 rs1799971 (A-G or G-G) would show greater pain variability. We expected to see the same pattern for these SNPs with regard to moderation (i.e., exacerbation) of the activity-pain association. METHODS:A total of 120 knee OA patients reported on their pain 3 times per day over 22 days using handheld computers, and wore an accelerometer to capture daily physical activity. Multilevel modeling was used to examine the magnitude of within-person variability in pain by genetic group. We also examined whether lagged, within-patient associations between level of activity in the afternoon (i.e., minutes of moderate intensity activity, and number of steps) and knee pain at the end-of-day were moderated by between-patient differences in genotype. RESULTS:Regarding OPRM1 rs1799971 (Asn40Asp), patients with two copies of the Asn40 allele showed the greatest day-to-day pain variability. Regarding COMT rs4680 (Val158Met), patients with the Val/Val genotype showed the greatest pain variability and also experienced the greatest increase in pain as a result of physical activity. A similar pattern of findings across bi-directional temporal lags was consistent with a negative feedback loop between daily physical activity and pain according to genotype. Consistent with some previous studies, there were no significant between-person differences in daily pain when comparing patients according to COMT rs4680, or OPRM1 rs1799971. CONCLUSION:This study provides preliminary evidence that patients with certain genotypes for COMT rs4680 and OPRM1 rs1799971 (G-G and A-A, respectively) experience more variability in their day-to-day pain and exacerbation of pain after daily physical activity compared to patients with other genotypes. Our findings should be replicated in larger study populations. IMPLICATIONS:Previous clinical research has focused primarily on differences in average level of pain between patients with and without a specific genotype. Assessment of within-person variability through repeated measurements in daily life enhances the reliability, power, and ecological validity of phenotypic measurement.

Dataset Information

Ethnicity interacts with the OPRM1 gene in experimental pain sensitivity.

Publications

Ethnicity interacts with the OPRM1 gene in experimental pain sensitivity.

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