Background

Osteoarthritis (OA) is a common progressive joint disease in dogs and cats. The goal of OA treatment is to reduce inflammation, minimize pain, and maintain joint function. Currently, non-steroidal anti-inflammatory drugs (e.g., meloxicam) are the cornerstone of treatment for OA pain, but side effects with long-term use pose important challenges to veterinary practitioners when dealing with OA pain. Palmitoylethanolamide (PEA) is a naturally-occurring fatty acid amide, locally produced on demand by tissues in response to stress. PEA endogenous levels change during inflammatory and painful conditions, including OA, i.e., they are typically increased during acute conditions and decreased in chronic inflammation. Systemic treatment with PEA has anti-inflammatory and pain-relieving effects in several disorders, yet data are lacking in OA. Here we tested a new composite, i.e., PEA co-ultramicronized with the natural antioxidant quercetin (PEA-Q), administered orally in two different rat models of inflammatory and OA pain, namely carrageenan paw oedema and sodium monoiodoacetate (MIA)-induced OA. Oral treatment with meloxicam was used as benchmark.

Conclusion

The present findings shed new light on some of the inflammatory and nociceptive pathways and mediators targeted by PEA-Q and confirm its anti-inflammatory and pain-relieving effects in rodent OA pain models. The translatability of these observations to canine and feline OA pain is currently under investigation.

Conclusions

PEA-Q is a novel co-ultramicronized formulation of PEA and quercetin whose effects were investigated in two pre-clinical models of OA pain in rats. Oral administration of PEA-Q decreased pain sensitivity, improved locomotor function, reduced inflammatory signs and mediators and lowered histological damage score. Although the underlying mechanism(s) of the observed effects are beyond the scope of our study, the particular cellular targets of PEA (e.g., mast cells and microglia) [19], redundancy of its receptors (direct and direct agonism on nuclear and membrane cannabinoid receptors) [14] and oxidative stress addressed by quercetin [22, 37] comprise targets that could be different from standard pharmacological tools (i.e., NSAIDs). Importantly, toxicological studies show that micronized and ultramicronized PEA is safe, the LD50 being greater than 2000 mg/kg [53]. Individually or in association with different antioxidant polyphenols, micronized and ultramicronized PEA has a long track record of use in human and veterinary patients, with good-to-excellent tolerability [14]. Moreover, prolonged use of PEA is not associated with the development of tolerance [43, 54]. There is an unmet need in veterinary medicine for the development of new agents to treat OA-associated pain which target alternative mechanisms distinct from currently approved drugs. The collective observations presented here propose that PEA-Q shows promise for multimodal pain management in canine and feline OA.”

Full Study:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541643/