Aims: To analyze in a population from Argentina the variation of three genes involved in the control of pain pathways-two genes that code for opioid receptors (OPRM1 and OPRK1) and COMT, which codes for an important enzyme in the control of neurotransmission-and to evaluate the associations of these genes with oral pain and the need for analgesics in the population under study. Methods: A total of 134 volunteer donors from the city of Resistencia and 27 donors from the Wichí community for comparison were analyzed for 13 single nucelotide polymorphisms (SNPs) and 1 insertion/deletion (Indel) localized in the three genes using polymerase chain reaction-restriction fragment length polymorphism or standard PCR and electrophoresis. All 134 individuals from Resistencia provided biologic samples for DNA analysis, and a subset (n = 81) agreed to answer a questionnaire for an association analysis. Statistical tests for a possible association between genetic variation and self-reported ethnic origin, oral pain, and need for analgesic drugs were performed. Results: Significant differences were found when the study population was compared to populations from other continents, as well as between the two studied populations (P .05). A positive association was suggested for the COMT gene from Resistencia with both oral pain intensity and analgesic requirements. Conclusion: The admixture process that occurred in the past of Resistencia probably contributed to a genetic differentiation in this population, and this genetic variation might influence phenotypic expressions of pain perception and analgesic requirements. Keywords: admixed population, pain genetics, pain perception, single nucleotide polymorphisms