Palmitoylethanolamide and Related ALIAmides: Prohomeostatic Lipid Compounds for Animal Health and Wellbeing

Abstract

Virtually every cellular process is affected by diet and this represents the foundation of dietary management to a variety of small animal disorders. Special attention is currently being paid to a family of naturally occurring lipid amides acting through the so-called autacoid local injury antagonism, i.e., the ALIA mechanism. The parent molecule of ALIAmides, palmitoyl ethanolamide (PEA), has being known since the 1950s as a nutritional factor with protective properties. Since then, PEA has been isolated from a variety of plant and animal food sources and its proresolving function in the mammalian body has been increasingly investigated. The discovery of the close interconnection between ALIAmides and the endocannabinoid system has greatly stimulated research efforts in this field. The multitarget and highly redundant mechanisms through which PEA exerts prohomeostatic functions fully breaks with the classical pharmacology view of “one drug, one target, one disease”, opening a new era in the management of animals’ health, i.e., an according-to-nature biomodulation of body responses to different stimuli and injury. The present review focuses on the direct and indirect endocannabinoid receptor agonism by PEA and its analogues and also targets the main findings from experimental and clinical studies on ALIAmides in animal health and wellbeing.

Dietary Supplementation with Palmitoyl-Glucosamine Co-Micronized with Curcumin Relieves Osteoarthritis Pain and Benefits Joint Mobility

“…Actually, several evidences support the use of curcumin in OA, mainly based on antioxidant in vitro property and a few clinical studies in humans and dogs, all performed with highly available formulations [ 37 , 59 , 60 , 61 ]. Most notably, PGA—especially in the micronized form—not only relieves inflammation and pain [ 23 , 30 , 33 ], but also exerts an entourage effect on endocannabinoids and related ALIAmides (e.g., PEA), as suggested by some preliminary observations [ 62 ]. The endocannabinoid system is now emerging as a pivotal player in joint functioning and its alterations contribute to OA pathology [ 48 , 63 , 64 ].…”

“…Recently, the endocannabinoid system is gaining increasing interest in veterinary medicine, particularly in the field of OA [ 21 ]. In this context, one of the most studied endocannabinoid-like substances is palmitoyl-ethanolamide (PEA) [ 22 ], an endogenous as well as foodborne compound, emerging as a promising dietary approach to inflammatory and/or painful disorders of the dog and cat [ 23 ]. PEA is the parent molecule of ALIAmides, i.e., a family of fatty acid amides acting through the so-called “autacoid local injury antagonism” (i.e., the ALIA mechanism) aimed at downmodulating hyperreactive cells (e.g.…”

“…PEA is the parent molecule of ALIAmides, i.e., a family of fatty acid amides acting through the so-called “autacoid local injury antagonism” (i.e., the ALIA mechanism) aimed at downmodulating hyperreactive cells (e.g. mast cells, microglia) [ 23 ]. Locally produced PEA has long been known to participate in the intrinsic control of pain [ 24 ] and to exert a tonic inhibitory control over the induction of nociceptive responses [ 25 ].…”

ALIAmides Update: Palmitoylethanolamide and Its Formulations on Management of Peripheral Neuropathic Pain

“…In fact, PEA has also been found in the seeds of some varieties of legumes, such as peas and beans, as well as in some varieties of vegetables, such as tomatoes and potatoes. Finally, high levels of PEA were also found in human, bovine, and moose milk [111][112][113].…”

“…The reduction of particle size highly and significantly increased both bioavailability and pain-relieving effect [175,176]. Finally, a novel compound developed by co-micronizing PGA and curcumin was found to regulate pain sensitivity, reducing allodynia, joint pain, and improving locomotor function in MIA-injected animals [113]. Clinical studies in human and veterinary patients are warranted to further evaluate therapeutic potential for PGA and m-PGA in in management of pain.…”