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Although many studies have reported disruptions in stress and reward cue\u2010elicited neural reactivity and heightened alcohol craving in individuals with AUD, little is known about these constructs among patients who experience pain. Here, individuals with pain (Pain+, <jats:italic>n<\/jats:italic>\u00a0=\u200931) and without pain (Pain\u2212, <jats:italic>n<\/jats:italic>\u00a0=\u200937) completed a well\u2010validated functional magnetic resonance imaging (fMRI) paradigm involving stress (S), alcohol (A) and neutral (N) cue exposure with repeated alcohol craving assessments. Using whole\u2010brain, voxel\u2010based analyses (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001, whole\u2010brain cluster correction at <jats:italic>\u03b1<\/jats:italic>\u00a0&lt;\u2009.05), the Pain+ versus Pain\u2212 group evidenced greater dorsal anterior cingulate cortex and left amygdala hyperactivation during N, but hypoactivation during the S\u2010N contrast. Additionally, Pain+ exhibited blunted right anterior insular cortex (AIC) during S\u2010N and blunted anteromedial thalamus and left AIC with hyperactive orbitofrontal cortex (OFC) during A\u2010N. Exploratory analyses further revealed that individuals with pain and AUD (<jats:italic>n<\/jats:italic>\u00a0=\u200917) relative to pain alone (<jats:italic>n<\/jats:italic>\u00a0=\u200914) showed hyperactive bilateral AIC and hypoactive right dorsal caudate during A\u2010N. Alcohol cue\u2010induced craving, significantly higher in Pain+ (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.03), correlated with blunted right AIC and OFC responses during A\u2010N. In sum, these results provide first evidence of heightened alcohol cue\u2010elicited craving and disrupted stress\u2010 and alcohol cue\u2010reactivity within corticostriatal\u2010limbic regions implicated in negative affect and preoccupation\/anticipation stages of AUD in those with pain and with comorbid pain and AUD. Future investigations of pain\u2010AUD interaction are needed that include systematic pain assessment and longitudinal designs with larger sample sizes.<\/jats:p>","DOI":"10.1111\/adb.70010","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T18:44:27Z","timestamp":1733942667000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Neural responses to stress and alcohol cues in individuals with pain with and without alcohol use disorder"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3980-591X","authenticated-orcid":false,"given":"Milena","family":"Radoman","sequence":"first","affiliation":[{"name":"Yale Stress Center, Department of Psychiatry Yale University School of Medicine, Yale Stress Center  New Haven Connecticut USA"},{"name":"Department of Radiology and Biomedical Imaging Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colleen","family":"McGowan","sequence":"additional","affiliation":[{"name":"Yale Stress Center, Department of Psychiatry Yale University School of Medicine, Yale Stress Center  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Heilner","sequence":"additional","affiliation":[{"name":"Yale Stress Center, Department of Psychiatry Yale University School of Medicine, Yale Stress Center  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheryl","family":"Lacadie","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3012-4349","authenticated-orcid":false,"given":"Rajita","family":"Sinha","sequence":"additional","affiliation":[{"name":"Yale Stress Center, Department of Psychiatry Yale University School of Medicine, Yale Stress Center  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,12,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.14260"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360\u20100443.2007.01759.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2018.05.009"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526\u20104637.2008.00420.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2018.04.013"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360\u20100443.2008.02358.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11606\u2010016\u20103586\u20105"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2012.07.010"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1441.030"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.120.000083"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12320"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2020.19070703"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2013.762"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2021.109253"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.11.027"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1204471"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2014.05.015"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3494\u201014.2015"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010020\u20101142\u20107"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agz067"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.35946\/arcr.v41.1.14"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12415"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2021.06.031"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14211"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1600965113"},{"key":"e_1_2_9_27_1","volume-title":"Structured clinical interview for DSM\u20105\u2010research version (SCID\u20105 for DSM\u20105, research version; 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