{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T16:07:47Z","timestamp":1773850067045,"version":"3.50.1"},"reference-count":61,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CINVESTAV"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Studies performed in a mouse model of chronic inflammatory pain induced by intraplantar injection of complete Freund\u2019s adjuvant (CFA) have shown that constitutive activation of the endogenous opioid signaling, besides serving as a mechanism of endogenous analgesia that tonically represses pain sensitization, also generates a state of endogenous opioid dependence. Since species-related differences concerning pain biology and addictive behaviors occur between mice and rats, the present study explored whether the coexistence of endogenous opioid analgesia and endogenous opioid dependence also characterizes a homologous rat model. To this aim, CFA-injured Wistar rats were treated with either 3 mg\/kg or 10 mg\/kg of the opioid receptor inverse agonist naltrexone (NTX) during the pain remission phase and monitored for 60 min for possible withdrawal behaviors. At 3 mg\/kg, NTX, besides inducing the reinstatement of mechanical allodynia, also caused a distinct appearance of ptosis, with slight but nonsignificant changes to the occurrence of teeth chatters and rearing. On the other hand, 10 mg\/kg of NTX failed to unmask pain sensitization and induced significantly lower levels of ptosis than 3 mg\/kg. Such an NTX-related response pattern observed in the rat CFA model seems to differ substantially from the pattern previously described in the mouse CFA model. This supports the knowledge that mice and rats are not identical in terms of pharmacological response and stresses the importance of choosing the appropriate species for preclinical pain research purposes depending on the scientific question being asked.<\/jats:p>","DOI":"10.3390\/ijms24032812","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T02:21:12Z","timestamp":1675304472000},"page":"2812","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Evidence for Endogenous Opioid Dependence Related to Latent Sensitization in a Rat Model of Chronic Inflammatory Pain"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8712-2400","authenticated-orcid":false,"given":"Julio C\u00e9sar","family":"Morales-Medina","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n en Reproducci\u00f3n Animal, CINVESTAV-Universidad Aut\u00f3noma de Tlaxcala, AP 62, Tlaxcala 90000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9342-9516","authenticated-orcid":false,"given":"Nicola","family":"Pugliese","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Bari, 70010 Valenzano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8122-9170","authenticated-orcid":false,"given":"Alessandro","family":"Di Cerbo","sequence":"additional","affiliation":[{"name":"School of Biosciences and Veterinary Medicine, University of Camerino, 62024 Matelica, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Zizzadoro","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Bari, 70010 Valenzano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4758-0562","authenticated-orcid":false,"given":"Tommaso","family":"Iannitti","sequence":"additional","affiliation":[{"name":"Section of Experimental Medicine, Department of Medical Sciences, University of Ferrara, Via Fossato di Mortara 70, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.jpain.2008.05.005","article-title":"Common chronic pain conditions in developed and developing countries: Gender and age differences and comorbidity with depression-anxiety disorders","volume":"9","author":"Tsang","year":"2008","journal-title":"J. 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