{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:54:25Z","timestamp":1790841265623,"version":"4.1.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Millions of chronic pain patients are managed with opioids, yet the neuropsychological implications of stable long-term daily opioid consumption remain unknown.<\/jats:p>\n                  <jats:p>Here, we contrasted the psychosocial profiles and brain structure and function of 70 chronic back pain patients prescribed opioids (CBP+O, average current daily opioid exposure of 7.8 years) with tightly matched 70 opioid-na\u00efve patients (CBP\u2212O) and 30 healthy subjects.<\/jats:p>\n                  <jats:p>Despite CBP+O exhibiting only modestly worse psychosocial profiles and small differences in brain morphology relative to CBP\u2212O, CBP+O showed stark differences in brain activity (ALFF). A large portion (38% of the variance) of this pattern was captured by a model using 19 receptor\/transporter distributions. The patients\u2019 (across all 140 CBP) psychosocial profiles were summarized by three principal components (PCs, explaining 70% of variance): functional disability, pain quality, and negative affect. These PCs were respectively associated with serotonergic (5HT1a and 5HT6) and opioidergic (mu-opioid receptor, MOR) receptor-related activities. In additional analyses and new data, 5HT1a- and MOR-related activities tracked opioid dose, abstinence status, and tapering success, while 5HT6-related activity tracked pain intensity.<\/jats:p>\n                  <jats:p>Overall, our findings uncover molecularly defined brain circuits in opioid use and chronic pain.<\/jats:p>","DOI":"10.1093\/brain\/awag339","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:59:26Z","timestamp":1790769566000},"source":"Crossref","is-referenced-by-count":0,"title":["Multi-molecular adaptations of long-term opioid use in chronic pain"],"prefix":"10.1093","author":[{"given":"Marwan N","family":"Baliki","sequence":"first","affiliation":[{"name":"Center for Translational Pain Research, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Department of Physical Medicine and Rehabilitation, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Shirley Ryan AbilityLab , Chicago, IL 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D","family":"Vigotsky","sequence":"additional","affiliation":[{"name":"Center for Translational Pain Research, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Departments of Biomedical Engineering and Statistics & Data Science, Northwestern University , Evanston, IL 60208 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaelle","family":"Rached","sequence":"additional","affiliation":[{"name":"Center for Translational Pain Research, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Department of Neuroscience, Northwestern University , Chicago, IL 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rami","family":"Jabakhanji","sequence":"additional","affiliation":[{"name":"Center for Translational Pain Research, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Department of Neuroscience, Northwestern University , Chicago, IL 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lejian","family":"Huang","sequence":"additional","affiliation":[{"name":"Center for Translational Pain Research, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Department of Neuroscience, Northwestern University , Chicago, IL 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo","family":"Branco","sequence":"additional","affiliation":[{"name":"Center for Translational Pain Research, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Department of Neuroscience, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Department of Anesthesia, Northwestern University , Chicago, IL 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Barroso","sequence":"additional","affiliation":[{"name":"Center for Translational Pain Research, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Department of Neuroscience, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Department of Anesthesia, Northwestern University , Chicago, IL 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Cong","sequence":"additional","affiliation":[{"name":"Center for Translational Pain Research, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Department of Neuroscience, Northwestern University , Chicago, IL 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Centeno","sequence":"additional","affiliation":[{"name":"Center for Translational Pain Research, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Department of Neuroscience, Northwestern University , Chicago, IL 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Cermak","sequence":"additional","affiliation":[{"name":"Center for Translational Pain Research, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Department of Neuroscience, Northwestern University , Chicago, IL 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Griffith","sequence":"additional","affiliation":[{"name":"Center for Translational Pain Research, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Medical and Social Sciences, Northwestern University , Chicago, IL 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6394-6077","authenticated-orcid":false,"given":"Ajay D","family":"Wasan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, School of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J","family":"Schnitzer","sequence":"additional","affiliation":[{"name":"Center for Translational Pain Research, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Department of Physical Medicine and Rehabilitation, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Department of Anesthesia, Northwestern University , Chicago, IL 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apkar Vania","family":"Apkarian","sequence":"additional","affiliation":[{"name":"Center for Translational Pain Research, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Department of Physical Medicine and Rehabilitation, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Department of Neuroscience, Northwestern University , Chicago, IL 60611 ,","place":["USA"]},{"name":"Department of Anesthesia, Northwestern University , Chicago, IL 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,1]]},"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awag339\/71544843\/awag339.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awag339\/71544843\/awag339.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:54:10Z","timestamp":1790837650000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/advance-article\/doi\/10.1093\/brain\/awag339\/8857160"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/brain\/awag339","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,1]]},"article-number":"awag339"}}