{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T14:05:49Z","timestamp":1779372349737,"version":"3.53.1"},"posted":{"date-parts":[[2026,5,18]]},"group-title":"Pharmacology and Toxicology","reference-count":114,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute on Drug Abuse, Bethesda, US","award":["U01 DA044451"],"award-info":[{"award-number":["U01 DA044451"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Opioid withdrawal is associated with heightened pain sensitivity, including allodynia. Although opioid-induced allodynia is well-documented in humans and animal models, the relationship between the severity of opioid withdrawal-induced allodynia and individual addiction-like behaviors remains poorly understood. To address this gap, Heterogeneous Stock rats underwent long access (12 hours\/day) intravenous oxycodone self-administration, followed by measurement of mechanical sensitivity at six timepoints across three weeks of abstinence. Rats were stratified by an Addiction Index derived from individual differences in the escalation of oxycodone intake, motivation to consume oxycodone, tolerance to oxycodone\u2019s analgesic effects, and acute withdrawal-induced mechanical pain sensitivity. Here, we show that oxycodone withdrawal induces significant and prolonged allodynia for up to three weeks, with High Addiction Index rats exhibiting greater intensity and longer duration of pain sensitivity than Low Addiction Index rats. Results remained consistent even when excluding allodynia from the Addiction Index, highlighting the robustness of the association between addiction-like severity and protracted allodynia. Linear regression associations revealed that self-administration behaviors, particularly oxycodone intake escalation and motivation to seek oxycodone, predicted subsequent withdrawal-induced allodynia severity. These findings demonstrate that greater addiction-like severity is associated with more intense and prolonged withdrawal-induced pain, supporting mechanical allodynia as a marker of addiction severity. These results motivate future work to define the mechanisms linking addiction severity to protracted opioid withdrawal-induced pain, with the goal of informing targeted clinical interventions for individuals most susceptible to severe abstinence-related allodynia.<\/jats:p>","DOI":"10.64898\/2026.05.14.725258","type":"posted-content","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:30:28Z","timestamp":1779150628000},"source":"Crossref","is-referenced-by-count":0,"title":["Addiction-Like Severity Predicts Prolonged Oxycodone Withdrawal-Induced Allodynia in Genetically Diverse Rats"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5452-7508","authenticated-orcid":false,"given":"Sonja L","family":"Plasil","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego, La Jolla CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lani","family":"Tieu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego, La Jolla CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengjia","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego, La Jolla CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego, La Jolla CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Sneddon","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego, La Jolla CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lieselot LG","family":"Carrette","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego, La Jolla CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly","family":"Brennan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego, La Jolla CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Morgan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego, La Jolla CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dyar","family":"Othman","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego, La Jolla CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego, La Jolla CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Foroutani","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego, La Jolla CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4782-7430","authenticated-orcid":false,"given":"Giordano","family":"de Guglielmo","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego, La Jolla CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marsida","family":"Kallupi","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego, La Jolla CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3700-5003","authenticated-orcid":false,"given":"Olivier","family":"George","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Diego, La Jolla CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026052106100891000_2026.05.14.725258v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(19)32229-9"},{"key":"2026052106100891000_2026.05.14.725258v1.2","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1186\/s12889-025-23283-1","article-title":"Global, regional, and national burden of opioid use disorder from 1990 to 2021: a statistical analysis of incidence, mortality, and disability-adjusted life years","volume":"25","year":"2025","journal-title":"BMC Public Health"},{"key":"2026052106100891000_2026.05.14.725258v1.3","unstructured":"Substance Abuse and Mental Health Services Administration Key substance use and mental health indicators in the United States: Results from the 2023 National Survey on Drug Use and Health. 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