{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:48:08Z","timestamp":1788922088390,"version":"build-2803163510"},"reference-count":68,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Education, University and Research (MIUR)"},{"name":"University of Florence"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Long-term opioid therapies are severely limited by the development of analgesic tolerance and gastrointestinal side effects. Camelina sativa, a plant of the Brassicaceae family, modulates the activity of peroxisome proliferator-activated receptor \u03b1 (PPAR-\u03b1 receptor), which is involved in the regulation of pain processing and gut physiology. The aim of this study was to evaluate the efficacy of Camelina sativa defatted seed meal (DSM) supplementation on the development of analgesic tolerance and side effects after repeated treatment with morphine in na\u00efve mice. Co-administering Camelina sativa DSM (1 g kg\u22121 p.o.) and morphine (10 mg kg\u22121 s.c.) increased the efficacy and duration of the opioid-induced acute analgesic effect. Camelina supplementation also delayed the onset of tolerance to the morphine analgesic effect. The same result was obtained through either simultaneously administering morphine and camelina or administering camelina 24 h before morphine injection for the entire duration of the experiment. Camelina also counteracted intestinal damage and visceral hypersensitivity caused by morphine treatment. The beneficial effects of camelina on morphine-related analgesic efficacy and gut side effects were prevented via pre-treatment with the PPAR-\u03b1 antagonist GW6471, though the latter did not influence the development of morphine tolerance. In conclusion, Camelina sativa DSM could be used as a supplement to improve the therapeutic profile of morphine.<\/jats:p>","DOI":"10.3390\/ijms26062519","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T16:39:03Z","timestamp":1741711143000},"page":"2519","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Benefits of Camelina sativa Supplementation in Morphine Treatment: Enhanced Analgesia, Delayed Tolerance and Reduced Gut Side Effects Through PPAR-\u03b1 Receptor Engagement"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3459-2660","authenticated-orcid":false,"given":"Elena","family":"Lucarini","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research, and Child Health\u2014NEUROFARBA, Pharmacology and Toxicology Section, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9477-1724","authenticated-orcid":false,"given":"Eleonora","family":"Pagnotta","sequence":"additional","affiliation":[{"name":"CREA\u2014Council for Agricultural Research and Economics, Research Centre for Cereal and Industrial Crops, 40128 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8834-5801","authenticated-orcid":false,"given":"Laura","family":"Micheli","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research, and Child Health\u2014NEUROFARBA, Pharmacology and Toxicology Section, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuele","family":"Trisolini","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research, and Child Health\u2014NEUROFARBA, Pharmacology and Toxicology Section, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8588-8798","authenticated-orcid":false,"given":"Roberto","family":"Matteo","sequence":"additional","affiliation":[{"name":"CREA\u2014Council for Agricultural Research and Economics, Research Centre for Cereal and Industrial Crops, 40128 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5421-7630","authenticated-orcid":false,"given":"Laura","family":"Righetti","sequence":"additional","affiliation":[{"name":"CREA\u2014Council for Agricultural Research and Economics, Research Centre for Cereal and Industrial Crops, 40128 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2090-7107","authenticated-orcid":false,"given":"Alma","family":"Martelli","sequence":"additional","affiliation":[{"name":"Department of 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University of Pisa, 56126 Pisa, Italy"},{"name":"Interdepartmental Research Centre Nutraceuticals and Food for Health\u2014NUTRAFOOD, University of Pisa, 56126 Pisa, Italy"},{"name":"Interdepartmental Research Centre of Ageing Biology and Pathology, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8374-4432","authenticated-orcid":false,"given":"Lorenzo","family":"Di Cesare Mannelli","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research, and Child Health\u2014NEUROFARBA, Pharmacology and Toxicology Section, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Ghelardini","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research, and Child Health\u2014NEUROFARBA, Pharmacology and Toxicology Section, University of Florence, 50139 Florence, 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