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The current study aims to understand the contribution of genetic factors to the neural processing of pain. Focusing on the single\u2010nucleotide polymorphism (SNP) of opioid receptor mu 1 (OPRM1) <jats:italic>A<\/jats:italic><jats:sup><jats:italic>118<\/jats:italic><\/jats:sup><jats:italic>G<\/jats:italic> (rs1799971) and catechol\u2010O\u2010methyltransferase (COMT) <jats:italic>val<\/jats:italic><jats:sup><jats:italic>158<\/jats:italic><\/jats:sup><jats:italic>met<\/jats:italic> (rs4680), we investigated how the two pain genes affect pain processing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We integrated a genetic approach with functional neuroimaging. We extracted genomic DNA information from saliva samples to genotype the SNP of OPRM1 and COMT. We used a percept\u2010related model, in which two different levels of perceived pain intensities (\u201clow pain: mildly painful\u201d vs \u201chigh pain: severely painful\u201d) were employed as experimental stimuli.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Low pain involves a broader network relative to high pain. The distinct effects of pain genes were observed depending on the perceived pain intensity. The effects of low pain were found in supramarginal gyrus, angular gyrus, and anterior cingulate cortex (ACC) for OPRM1 and in middle temporal gyrus for COMT. For high pain, OPRM1 affected the insula and cerebellum, while COMT affected the middle occipital gyrus and ACC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>OPRM1 primarily affects sensory and cognitive components of pain processing, while COMT mainly influences emotional aspects of pain processing. The interaction of the two pain genes was associated with neural patterns coding for high pain and neural activation in the ACC in response to pain. The proteins encoded by the OPRM1 and COMT may contribute to the firing of pain\u2010related neurons in the human ACC, a critical center for subjective pain experience.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pcn.13648","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T05:25:00Z","timestamp":1708925100000},"page":"300-308","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of functional polymorphisms of opioid receptor mu 1 and <scp>catechol\u2010O<\/scp>\u2010methyltransferase on the neural processing of pain"],"prefix":"10.1111","volume":"78","author":[{"given":"Yongjeon","family":"Cheong","sequence":"first","affiliation":[{"name":"Cognitive Science Research Group Korea Brain Research Institute  Daegu Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seonkyoung","family":"Lee","sequence":"additional","affiliation":[{"name":"Cognitive 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