{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:51:07Z","timestamp":1790661067155,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,16]],"date-time":"2022-10-16T00:00:00Z","timestamp":1665878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Chronic low back pain (CLBP) due to osteoarthritis represents a therapeutic challenge worldwide. Opioids are extensively used to treat such pain, but the development of tolerance, i.e., less susceptibility to the effects of the opioid, which can result in a need for higher doses to achieve the same analgesic effect, may limit their use. Animal models suggest that ultra-low doses of opioid antagonists combined with opioid agonists can decrease or block the development of opioid tolerance. In this retrospective study, we tested this hypothesis in humans. In 2019, 53 patients suffering from CLBP were treated with either Oxycodone and Naloxone Prolonged Release (27 patients, OXN patients) or Oxycodone Controlled Release (26 patients, OXY patients). The follow-up period lasted 2 years, during which 10 patients discontinued the treatment, 5 out of each group. The remaining 43 patients reached and maintained the targeted pain relief, but at 18 and 24 months, the OXY patients showed a significantly higher oxycodone consumption than OXN patients to reach the same level of pain relief. No cases of respiratory depression or opioid abuse were reported. There were no significant differences in the incidence of adverse effects between the two treatments, except for constipation, more common in OXY patients. From our results, we can affirm that a long-term opioid treatment with oxycodone-naloxone combination, when compared with oxycodone only, may significantly hinder the development of opioid tolerance. We were also able to confirm, in our cohort, the well known positive effect of naloxone in terms of opioid-induced bowel dysfunction incidence reduction.<\/jats:p>","DOI":"10.3390\/ijerph192013354","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:04:55Z","timestamp":1665965095000},"page":"13354","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Oxycodone-Naloxone Combination Hinders Opioid Consumption in Osteoarthritic Chronic Low Back Pain: A Retrospective Study with Two Years of Follow-Up"],"prefix":"10.3390","volume":"19","author":[{"given":"Enrico","family":"Polati","sequence":"first","affiliation":[{"name":"Anesthesiology, Intensive Care and Pain Therapy Centre, Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37124 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6175-0620","authenticated-orcid":false,"given":"Marta","family":"Nizzero","sequence":"additional","affiliation":[{"name":"Anesthesiology, Intensive Care and Pain Therapy Centre, Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37124 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacopo","family":"Rama","sequence":"additional","affiliation":[{"name":"Anesthesiology, Intensive Care and Pain Therapy Centre, Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37124 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvise","family":"Martini","sequence":"additional","affiliation":[{"name":"Anesthesiology, Intensive Care and Pain Therapy Centre, Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37124 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Gottin","sequence":"additional","affiliation":[{"name":"Anesthesiology, Intensive Care and Pain Therapy Centre, Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37124 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7053-8434","authenticated-orcid":false,"given":"Katia","family":"Donadello","sequence":"additional","affiliation":[{"name":"Anesthesiology, Intensive Care and Pain Therapy Centre, Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37124 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Del Balzo","sequence":"additional","affiliation":[{"name":"Department of Medicine and Public Health, Section of Forensic Medicine, University of Verona, 37124 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3822-2923","authenticated-orcid":false,"given":"Giustino","family":"Varrassi","sequence":"additional","affiliation":[{"name":"Paolo Procacci Foundation, 00193 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Marinangeli","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2377-3765","authenticated-orcid":false,"given":"Alessandro","family":"Vittori","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Critical Care, ARCO, Ospedale Pediatrico Bambino Ges\u00f9 IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Secchettin","sequence":"additional","affiliation":[{"name":"Anesthesiology, Intensive Care and Pain Therapy Centre, Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37124 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorio","family":"Schweiger","sequence":"additional","affiliation":[{"name":"Anesthesiology, Intensive Care and Pain Therapy Centre, Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37124 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1097\/j.pain.0000000000000160","article-title":"A classification of chronic pain for ICD-11","volume":"156","author":"Treede","year":"2015","journal-title":"Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3401","DOI":"10.2147\/JPR.S328434","article-title":"Pursuing the Recovery of Severe Chronic Musculoskeletal Pain in Italy: Clinical and Organisational Perspectives from a SIAARTI Survey","volume":"14","author":"Vittori","year":"2021","journal-title":"J. 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