{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:09:41Z","timestamp":1792631381077,"version":"4.5.0"},"reference-count":41,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T00:00:00Z","timestamp":1681084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"publisher","award":["AC220035"],"award-info":[{"award-number":["AC220035"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"publisher","award":["21K20983"],"award-info":[{"award-number":["21K20983"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"publisher","award":["22ek0610028h0001"],"award-info":[{"award-number":["22ek0610028h0001"]}],"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":["AC220035"],"award-info":[{"award-number":["AC220035"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21K20983"],"award-info":[{"award-number":["21K20983"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["22ek0610028h0001"],"award-info":[{"award-number":["22ek0610028h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Autotaxin, encoded by the ENPP2 gene, is a known key element of neuropathic pain; however, its involvement in nociceptive pain processing remains unclear. We explored the associations between postoperative pain intensity, 24-h postoperative opioid dose requirements, and 93 ENNP2-gene single-nucleotide polymorphisms (SNPs) in 362 healthy patients who underwent cosmetic surgery using the dominant, recessive, and genotypic models. Next, we validated the associations between relevant SNPs on the one hand and pain intensity and daily opioid dosages on the other in 89 patients with cancer-related pain. In this validation study, a Bonferroni correction for multiplicity was applied on all relevant SNPs of the ENPP2 gene and their respective models. In the exploratory study, three models of two SNPs (rs7832704 and rs2249015) were significantly associated with postoperative opioid doses, although the postoperative pain intensity was comparable. In the validation study, the three models of the two SNPs were also significantly associated with cancer pain intensity (p &lt; 0.017). Patients with a minor allele homozygosity complained of more severe pain compared with patients with other genotypes when using comparable daily opioid doses. Our findings might suggest that autotaxin is associated with nociceptive pain processing and the regulation of opioid requirements.<\/jats:p>","DOI":"10.3390\/ijms24086986","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T03:49:29Z","timestamp":1681098569000},"page":"6986","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genetic Polymorphisms of ENPP2 Are Possibly Associated with Pain Severity and Opioid Dose Requirements in Patients with Inflammatory Pain Conditions: Clinical Observation Study"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2274-7917","authenticated-orcid":false,"given":"Rikuhei","family":"Tsuchida","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Relief Center, The University of Tokyo Hospital, Hongo 7-3-1, Bunkyoku, Tokyo 113-8655, 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, Kami Kitazawa 2-1-6, Setagayaku, Tokyo 156-0057, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken-ichi","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Department of Oral Health and Clinical Science, Tokyo Dental College, Kanda Misakichou 2-9-18, Chiyodaku, Tokyo 101-0061, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Ichinohe","sequence":"additional","affiliation":[{"name":"Department of Dental Anesthesiology, Tokyo Dental College, Kanda Misakichou 2-9-18, Chiyodaku, Tokyo 101-0061, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4539-5750","authenticated-orcid":false,"given":"Kuniyuki","family":"Kano","sequence":"additional","affiliation":[{"name":"Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo 7-3-1, Bunkyoku, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Kurano","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, The University of Tokyo Hospital, Hongo 7-3-1, Bunkyoku, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8342-0278","authenticated-orcid":false,"given":"Kazutaka","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Kami Kitazawa 2-1-6, Setagayaku, Tokyo 156-0057, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3662-8217","authenticated-orcid":false,"given":"Masahiko","family":"Sumitani","sequence":"additional","affiliation":[{"name":"Department of Pain and Palliative Medicine, The University of Tokyo Hospital, Hongo 7-3-1, Bunkyoku, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Goldberg, D.S., and McGee, S.J. 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