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However, the neuropharmacological mechanisms by which unpredictable chronic stress (UCS) modulates nociception in translational vertebrate models remains poorly understood. Here, we characterized a zebrafish model of stress-induced sensitization to a visceral chemical challenge by exposing adult fish to a 7- or 14-day UCS protocol (UCS7\/UCS14) followed by intraperitoneal acetic acid (AA) injection (1.0\u20135.0% v\/v). In unstressed fish, AA at 1.0% remained subthreshold for inducing the characteristic writhing-like body curvature endpoint, whereas at 5.0% produced a robust response, hence validating the assay. In contrast, UCS exposure revealed a marked nociception-like response to AA 1.0%, reflected by increased body curvature index, indicating a lowered response threshold after chronic stress. Locomotor endpoints exhibited stress-dependent cross-over effects: AA at 1.0% decreased distance traveled in unstressed fish but increased locomotion and reduced immobility in UCS-exposed fish. Pharmacological validation (in UCS7) showed that morphine attenuated the UCS-sensitized body curvature response, whereas diclofenac did not, consistent with an opioidergic contribution to the nociception-like endpoint. Whole-body cortisol levels were elevated by UCS exposure (with or without AA 1.0%) and reduced by morphine in the UCS\u2009+\u2009AA condition, whereas diclofenac was inactive. Together, these findings establish a pharmacologically tractable adult zebrafish model of stress-induced sensitization with translational relevance for CNS-targeted analgesic discovery and mechanistic studies of stress\u2013pain comorbidity.<\/jats:p>","DOI":"10.1007\/s00702-026-03159-3","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T15:27:30Z","timestamp":1779809250000},"page":"1739-1754","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Opioidergic modulation of stress-induced hyperalgesia in adult zebrafish"],"prefix":"10.1007","volume":"133","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6218-9660","authenticated-orcid":false,"given":"Fabiano V.","family":"Costa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6285-3014","authenticated-orcid":false,"given":"Lana","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3229-9611","authenticated-orcid":false,"given":"Lucca K.","family":"Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Canzian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan V.","family":"Kalueff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis B.","family":"Rosemberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla D.","family":"Bonan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"3159_CR70","doi-asserted-by":"publisher","unstructured":"Altman R, Bosch B, Brune K, Patrignani P, Young C (2015) Advances in NSAID development: evolution of diclofenac products using pharmaceutical technology. 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