{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:51:50Z","timestamp":1791276710030,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22H04922"],"award-info":[{"award-number":["22H04922"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["23ek0610028h0002"],"award-info":[{"award-number":["23ek0610028h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropsychopharm Rep"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>G protein\u2013coupled receptors, the largest class of cell surface receptors, are ubiquitously expressed throughout the body. Different subtypes of G protein \u03b1 subunits activate distinct intracellular signaling pathways and mediate opioid analgesic effects. However, the contributions of these G\u03b1 subunits remain unclear. We conducted a hypothesis\u2010generating, two\u2010stage candidate gene association study to identify potential genetic loci related to pain processing and opioid analgesia, focusing on genes encoding G protein \u03b1 subunits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To identify candidate single\u2010nucleotide polymorphisms (SNPs) in seven genes encoding G protein \u03b1 subunits, we analyzed postoperative opioid consumption, pain intensity, and opioid responsiveness in two exploratory cohorts [laparoscopy\u2010assisted colectomy (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009350) and mandibular plastic surgery (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009354)]. For identified candidate SNPs, we further evaluated opioid responsiveness in a confirmatory cohort of 89 patients with cancer pain. We also conducted a preliminary sensitivity analysis adjusting for relevant covariates.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Two SNPs (rs10781468 in the\n                      <jats:italic>GNAQ<\/jats:italic>\n                      gene and rs308049 in the\n                      <jats:italic>GNA11<\/jats:italic>\n                      gene) showed significant associations in both exploratory cohorts. Patients with postoperative pain who were homozygous for the minor allele of rs10781468 exhibited higher opioid sensitivity or lower pain severity. In the confirmatory cohort, homozygosity for the major allele of rs10781468 was significantly associated with increased opioid sensitivity for cancer pain management under the dominant model (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.025) and the genotypic model (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.020), whereas rs308049 was not. The observed phenotypes and associated genetic models differed across cohorts, and sensitivity analyses continued to demonstrate some significant associations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>As a hypothesis\u2010generating investigation, we suggest that rs10781468 may serve as a potential candidate marker of responsiveness to opioid analgesics. Our findings should be validated in a large\u2010scale study with a homogeneous pain type in which the opioid administration protocol is controlled to further examine the association observed in this exploratory study.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/npr2.70148","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T11:56:26Z","timestamp":1782820586000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The rs10781468 Genetic Polymorphism of the G\u03b1q (\n                    <scp>GNAQ<\/scp>\n                    ) Gene Is Associated With Responsiveness to Opioid Analgesics in Patients With Postoperative and Cancer Pain: An Exploratory Study"],"prefix":"10.1002","volume":"46","author":[{"given":"Hiroaki","family":"Owada","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Relief Center The University of Tokyo Hospital  Bunkyo\u2010ku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8286-4651","authenticated-orcid":false,"given":"Daisuke","family":"Nishizawa","sequence":"additional","affiliation":[{"name":"Addictive Substance Project Tokyo Metropolitan Institute of Medical Science  Setagaya\u2010ku Tokyo Japan"},{"name":"Department of Neuropsychopharmacology National Institute of Mental Health, National Center of Neurology and Psychiatry  Kodaira\u2010shi Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Mieda","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Saitama Medical University Hospital  Saitama\u2010shi Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Tsujita","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Saitama Medical University International Medical Center  Hidaka\u2010shi Saitama 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Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken\u2010ichi","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Department of Oral Health and Clinical Science Tokyo Dental College  Chiyoda\u2010ku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Ichinohe","sequence":"additional","affiliation":[{"name":"Department of Dental Anesthesiology Tokyo Dental College  Chiyoda\u2010ku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazutaka","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Addictive Substance Project Tokyo Metropolitan Institute of Medical Science  Setagaya\u2010ku Tokyo Japan"},{"name":"Department of Neuropsychopharmacology National Institute of Mental Health, National Center of Neurology and Psychiatry  Kodaira\u2010shi Tokyo 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