Association between human μ-opioid receptor gene polymorphism, pain tolerance, and opioid addiction

Central to both pain responses and opioid addiction is activity at the mu-opioid receptor. To explore the role of the mu-opioid receptor gene (OPRM) in human pain tolerance and opioid addiction, we examined the relationships among OPRM genotype and experimental pain tolerance in opioid addicts in methadone treatment (n = 50) and healthy normal controls (n = 59). Pain phenotype (pain tolerant vs. pain intolerant) was operationalized as tolerance to a standardized noxious stimulus (either thermal or mechanical), and dichotomized based on distribution. One microsatellite and two single nucleotide polymorphisms, A118G and C17T, in exon 1 were typed to study the OPRM gene. Although the established relationship between the phenotypes of opioid addiction and pain intolerance was validated (P = 0.02), genotype differed neither between addict-affected vs. control, nor pain tolerant vs. intolerant subjects. The variant A118G was absent in all individuals and the C17T polymorphism appeared in only three African-American individuals (two addicts and one control). The absence of this polymorphism, the small sample size and the heterogeneous ethnic backgrounds of participants in the pilot study allow only tentative conclusions based on the results, thus the role of the opioid receptor in pain and opioid reward response remains uncertain. (C) 2003 Wiley-Liss, Inc.