{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T06:16:08Z","timestamp":1772604968389,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Surgical nerve injuries lead to persistent neuropathic pain (NP) in up to 30% of patients. Among many other factors, polymorphisms in the human leukocyte antigen (HLA) genes have been suggested to contribute to the development of neuropathic pain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed a genetic association analysis of HLA class I and class II alleles in women who had been operated on for breast cancer. Patients had a surgeon\u2010confirmed perioperative nerve injury and were examined 4\u20139\u2009years after their surgery. Patients with painful (cases,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200927) and painless (controls,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200930) intercostobrachial nerve resection were studied. Cases included patients with definite NP with worst pain intensity in the past week \u2265\u20094\/10 on a numerical rating scale (NRS) and controls had the same nerve injury with no NP or other pains. Whole\u2010genome single nucleotide polymorphism data were produced, and HLA class I (HLA\u2010A, \u2010B, \u2010C) and class II (HLA\u2010DRB1, \u2010DQA1, \u2010DQB1 and \u2010DPB1) alleles were determined by imputation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HLA\u2010DRB1*03:01, DQA1*05:01 and DQB1*02:01 alleles appeared to be associated with painful nerve injury after breast cancer surgery (nominal\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.007 for all, carriership OR\u2009=\u200912.0, 95% CI 1.38\u2013104; FDR corrected\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.07). These alleles comprise the DR3\u2010DQ2 haplotype, which is part of the ancestral haplotype AH8.1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results provide further support for the role of HLA genetic variation in the development of persistent post\u2010surgical neuropathic pain, which indirectly implies a mechanism involving immunological memory in this process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>We report a novel association between the HLA\u2010DR3\u2010DQ2 haplotype and the development of persistent neuropathic pain after breast cancer surgery. Our results provide further evidence for the role of HLA polymorphism in persistent neuropathic pain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejp.70009","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T09:14:07Z","timestamp":1741943647000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>HLA<\/scp>\n                    \u2010Region Genetic Association Analysis of Breast Cancer Patients With and Without Persistent Postsurgical Neuropathic Pain"],"prefix":"10.1002","volume":"29","author":[{"given":"L.","family":"Mustonen","sequence":"first","affiliation":[{"name":"Clinical Neurosciences, Neurology Helsinki University Hospital and University of Helsinki  Helsinki Finland"},{"name":"Department of Anaesthesiology, Intensive Care and Pain Medicine Helsinki University Hospital and University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. K.","family":"Nieminen","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences, Neurology Helsinki University Hospital and University of Helsinki  Helsinki Finland"},{"name":"Translational Immunology Research Program University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Koskela","sequence":"additional","affiliation":[{"name":"Department of Research and Development Finnish Red Cross Blood Service  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Kaunisto","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland (FIMM), HiLIFE University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Kalso","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Intensive Care and Pain Medicine Helsinki University Hospital and University of Helsinki  Helsinki Finland"},{"name":"SleepWell Research Program, University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. J.","family":"Tienari","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences, Neurology Helsinki University Hospital and University of Helsinki  Helsinki Finland"},{"name":"Translational Immunology Research Program University of Helsinki  Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Harno","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences, Neurology Helsinki University Hospital and University of Helsinki  Helsinki Finland"},{"name":"Department of Anaesthesiology, Intensive Care and Pain Medicine Helsinki University Hospital and University of Helsinki  Helsinki Finland"},{"name":"SleepWell Research Program, University of Helsinki  Helsinki 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