Chronic Pain in Dogs and Cats: Is There Place for Dietary Intervention with Micro-Palmitoylethanolamide?

SIMPLE SUMMARY: Chronic pain is being increasingly recognized and addressed in small animal practice. The recent recognition that inability to communicate does not negate the possibility to experience pain requires veterinarians to actively recognize, assess and manage animal pain. In order to successfully treat pain while limiting side effects, a combination of different therapeutic weapons (e.g., analgesic drugs, acupuncture, physiotherapy and dietary interventions) is currently preferred. In this perspective, the endocannabinoid-like palmitoylethanolamide represents a promising option, since it is naturally occurring in food sources and animal tissues, addresses the mechanisms of chronic pain (i.e., immune cell hyperactivity) and is presently used in complementary feeds for dogs and cats in highly absorbable micronized formulations (i.e., micro-palmitoylethanolamide). In the present paper, the role of immune non-neuronal cells in chronic pain is reviewed. Moreover, the function of body-own palmitoylethanolamide in controlling pain through non-neuronal cell modulation is discussed. Finally, data on pain-relieving effects provided by dietary supplementation with micro-palmitoylethanolamide are presented. The critical mass of data here reviewed might help veterinary practitioners in the process of evidence-based decision-making regarding the management of chronic pain in cats and dogs. ABSTRACT: The management of chronic pain is an integral challenge of small animal veterinary practitioners. Multiple pharmacological agents are usually employed to treat maladaptive pain including opiates, non-steroidal anti-inflammatory drugs, anticonvulsants, antidepressants, and others. In order to limit adverse effects and tolerance development, they are often combined with non-pharmacologic measures such as acupuncture and dietary interventions. Accumulating evidence suggests that non-neuronal cells such as mast cells and microglia play active roles in the pathogenesis of maladaptive pain. Accordingly, these cells are currently viewed as potential new targets for managing chronic pain. Palmitoylethanolamide is an endocannabinoid-like compound found in several food sources and considered a body’s own analgesic. The receptor-dependent control of non-neuronal cells mediates the pain-relieving effect of palmitoylethanolamide. Accumulating evidence shows the anti-hyperalgesic effect of supplemented palmitoylethanolamide, especially in the micronized and co-micronized formulations (i.e., micro-palmitoylethanolamide), which allow for higher bioavailability. In the present paper, the role of non-neuronal cells in pain signaling is discussed and a large number of studies on the effect of palmitoylethanolamide in inflammatory and neuropathic chronic pain are reviewed. Overall, available evidence suggests that there is place for micro-palmitoylethanolamide in the dietary management of chronic pain in dogs and cats.