Benefits of Camelina sativa Supplementation in Morphine Treatment: Enhanced Analgesia, Delayed Tolerance and Reduced Gut Side Effects Through PPAR-α Receptor Engagement

Long-term opioid therapies are severely limited by the development of analgesic tolerance and gastrointestinal side effects. <i>Camelina sativa</i>, a plant of the Brassicaceae family, modulates the activity of peroxisome proliferator-activated receptor α (PPAR-α receptor), which is involved in the regulation of pain processing and gut physiology. The aim of this study was to evaluate the efficacy of <i>Camelina sativa</i> defatted seed meal (DSM) supplementation on the development of analgesic tolerance and side effects after repeated treatment with morphine in naïve mice. Co-administering <i>Camelina sativa</i> DSM (1 g kg^-1 p.o.) and morphine (10 mg kg^-1 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-α antagonist GW6471, though the latter did not influence the development of morphine tolerance. In conclusion, <i>Camelina sativa</i> DSM could be used as a supplement to improve the therapeutic profile of morphine.