Background: Osteoarthritis (OA) is a common progressive joint disease in dogs and cats. The goal of OA treatment\nis to reduce inflammation, minimize pain, and maintain joint function. Currently, non-steroidal anti-inflammatory\ndrugs (e.g., meloxicam) are the cornerstone of treatment for OA pain, but side effects with long-term use pose\nimportant challenges to veterinary practitioners when dealing with OA pain. Palmitoylethanolamide (PEA) is a\nnaturally-occurring fatty acid amide, locally produced on demand by tissues in response to stress. PEA endogenous\nlevels change during inflammatory and painful conditions, including OA, i.e., they are typically increased during acute\nconditions and decreased in chronic inflammation. Systemic treatment with PEA has anti-inflammatory and\npain-relieving effects in several disorders, yet data are lacking in OA. Here we tested a new composite, i.e.,\nPEA co-ultramicronized with the natural antioxidant quercetin (PEA-Q), administered orally in two different rat\nmodels of inflammatory and OA pain, namely carrageenan paw oedema and sodium monoiodoacetate (MIA)-induced\nOA. Oral treatment with meloxicam was used as benchmark.\nResults: PEA-Q decreased inflammatory and hyperalgesic responses induced by carrageenan injection, as shown by: (i)\npaw oedema reduction, (ii) decreased severity in histological inflammatory score, (iii) reduced activity of myeloperoxidase,\ni.e., a marker of inflammatory cell infiltration, and (iv) decreased thermal hyperalgesia. Overall PEA-Q showed\nsuperior effects compared to meloxicam. In MIA-treated animals, PEA-Q exerted the following effects: (i) reduced\nmechanical allodynia and improved locomotor function, (ii) protected cartilage against MIA-induced histological\ndamage, and (iii) counteracted the increased serum concentration of tumor necrosis factor alpha, interleukin 1\nbeta, metalloproteases 1, 3, 9 and nerve growth factor. The magnitude of these effects was comparable to, or\neven greater than, those of meloxicam Conclusion: The present findings shed new light on some of the inflammatory and nociceptive pathways and\nmediators targeted by PEA-Q and confirm its anti-inflammatory and pain-relieving effects in rodent OA pain\nmodels. The translatability of these observations to canine and feline OA pain is currently under investigation.
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