{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:59:30Z","timestamp":1787018370684,"version":"build-2736575974"},"reference-count":97,"publisher":"American Society for Clinical Investigation","issue":"19","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["PJT-497592"],"award-info":[{"award-number":["PJT-497592"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100021570","name":"Strategy for Patient-Oriented Research","doi-asserted-by":"crossref","award":["SCA-145102"],"award-info":[{"award-number":["SCA-145102"]}],"id":[{"id":"10.13039\/100021570","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Inter- and intraindividual fluctuations in pain intensity pose a major challenge to treatment efficacy, with a majority of people perceiving their pain relief as inadequate. Recent preclinical studies have identified circadian rhythmicity as a potential contributor to these fluctuations and a therapeutic target.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We therefore sought to determine the impact of circadian rhythms in people with chronic low back pain (CLBP) through a detailed characterization, including questionnaires to evaluate biopsychosocial characteristics, ecological momentary assessment (7 day e-diaries at 8:00\/14:00\/20:00) to observe pain fluctuations, and intraday blood transcriptomics (at 8:00\/20:00) to identify genes\/pathways of interest.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>While most individuals displayed constant or variable\/mixed pain phenotypes, a distinct subset had daily fluctuations of increasing pain scores (&gt;30% change in intensity over 12 hours in \u22654\/7 days). This population had no opioid users, better biopsychosocial profiles, and differentially expressed transcripts relative to other pain phenotypes. The circadian-governed neutrophil degranulation pathway was particularly enriched among arrhythmic individuals; the link between neutrophil degranulation and opioid use was further confirmed in a separate CLBP cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Our findings identified pain rhythmicity and the circadian expression of neutrophil degranulation pathways as indicators of CLBP outcomes, which may help provide a personalized approach to phenotyping biopsychosocial characteristics and medication use. This highlights the need to better understand the impact of circadian rhythmicity across chronic pain conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>This work was funded by grants from the Canadian Institutes of Health Research (CIHR; grant PJT-190170, to NG and MGP) and the CIHR-Strategy for Patient-Oriented Research Chronic Pain Network (grant SCA-145102, to NG, QD, LD, MGP, and MC). DT was funded by a MS Canada endMS Doctoral Research Award, AMZ by an Ontario Graduate Scholarship, HGMG by a CIHR Doctoral Research Award, MGP by a Junior 2 Research Scholarship from the Fonds de recherche du Qu\u00e9bec \u2013 Sant\u00e9, and LD by a Canadian Excellence Research Chairs and Pfizer Canada Professorship in Pain Research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci188620","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T18:26:18Z","timestamp":1759256778000},"source":"Crossref","is-referenced-by-count":4,"title":["Circadian rhythmicity and biopsychosocial characteristics influence opioid use in chronic low back pain"],"prefix":"10.1172","volume":"135","author":[{"given":"Doriana","family":"Taccardi","sequence":"first","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University, Kingston, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda M.","family":"Zacharias","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University, Kingston, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailey G.M.","family":"Gowdy","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University, Kingston, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitra","family":"Knezic","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University, Kingston, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2924-5960","authenticated-orcid":true,"given":"Marc","family":"Parisien","sequence":"additional","affiliation":[{"name":"Faculty of Dental Medicine and Oral Health Sciences, Department of Anesthesia, Faculty of Medicine, Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne J.","family":"Bisson","sequence":"additional","affiliation":[{"name":"Kingston Health Sciences Centre, Kingston, Ontario, Canada."},{"name":"Department of Anesthesiology and Perioperative Medicine,"},{"name":"Centre for Neuroscience Studies, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi Yi","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University, Kingston, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara A.","family":"Stickley","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University, Kingston, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Brown","sequence":"additional","affiliation":[{"name":"Kingston Health Sciences Centre, Kingston, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daenis","family":"Camir\u00e9","sequence":"additional","affiliation":[{"name":"Kingston Health Sciences Centre, Kingston, Ontario, Canada."},{"name":"Department of Anesthesiology and Perioperative Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary","family":"Wilson","sequence":"additional","affiliation":[{"name":"Kingston Health Sciences Centre, Kingston, Ontario, Canada."},{"name":"Department of Anesthesiology and Perioperative Medicine,"},{"name":"School of Nursing, Queen\u2019s University, Kingston, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley N.","family":"Singer","sequence":"additional","affiliation":[{"name":"Chronic Pain Network, McMaster University, Hamilton, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Daly-Cyr","sequence":"additional","affiliation":[{"name":"Chronic Pain Network, McMaster University, Hamilton, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Choini\u00e8re","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada."},{"name":"Research Center of the Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihang","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, Queen\u2019s University, Kingston, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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