Palmitoylethanolamide, endocannabinoids and related cannabimimetic compounds in protection against tissue inflammation and pain: Potential use in companion animals

Re, G.; Barbero, Raffaella; Miolo, Alda; Marzo, Vincenzo Di

doi:10.1016/j.tvjl.2005.10.003

Cited by 175 publications

(168 citation statements)

References 88 publications

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“…The demonstration that, at least in cells, 15-LOX is capable of metabolizing 2-AG to 15-HETE-G (see references in Vandevoorde & Lambert [112]), which is a ligand for the antiinflammatory nuclear receptor PPARa [28], suggests that changes in LOX expression and metabolism of endocannabinoids via this pathway may also influence nociceptive processing. Indeed, we and others have shown that PPARa ligands can have marked inhibitory effects on inflammatory pain responses (see references in [113][114][115][116]). …”

Section: Effects Of Novel Biological Metabolites Of 2-ag and Anandamidementioning

confidence: 90%

Dynamic changes to the endocannabinoid system in models of chronic pain

Sagar

Burston

Woodhams

et al. 2012

Phil. Trans. R. Soc. B

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The analgesic effects of cannabinoid ligands, mediated by CB1 receptors are well established. However, the side-effect profile of CB1 receptor ligands has necessitated the search for alternative cannabinoid-based approaches to analgesia. Herein, we review the current literature describing the impact of chronic pain states on the key components of the endocannabinoid receptor system, in terms of regionally restricted changes in receptor expression and levels of key metabolic enzymes that influence the local levels of the endocannabinoids. The evidence that spinal CB2 receptors have a novel role in the modulation of nociceptive processing in models of neuropathic pain, as well as in models of cancer pain and arthritis is discussed. Recent advances in our understanding of the spinal location of the key enzymes that regulate the levels of the endocannabinoid 2-AG are discussed alongside the outcomes of recent studies of the effects of inhibiting the catabolism of 2-AG in models of pain. The complexities of the enzymes capable of metabolizing both anandamide (AEA) and 2-AG have become increasingly apparent. More recently, it has come to light that some of the metabolites of AEA and 2-AG generated by cyclooxygenase-2, lipoxygenases and cytochrome P450 are biologically active and can either exacerbate or inhibit nociceptive signalling.

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Section: Effects Of Novel Biological Metabolites Of 2-ag and Anandamidementioning

confidence: 90%

Dynamic changes to the endocannabinoid system in models of chronic pain

Sagar

Burston

Woodhams

et al. 2012

Phil. Trans. R. Soc. B

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“…Indeed, the anti-inflammatory properties of PEA were first described over fifty years ago (Coburn et al, 1954) and are well established Costa et al, 2002;De Petrocellis et al, 2001;Di Marzo et al, 2001b;Lo Verme et al, 2005a;Mazzari et al, 1996;Re et al,2007). PEA does not bind to CB 1 or CB 2 receptors (Di Marzo et al, 2001b;Lambert and Di Marzo, 1999;Lambert et al, 2002), however, SR144528 has been found to block the anti-edema effects of PEA that is administered before carrageenan Lichtman et al, 2004;Malan et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, it has been proposed that PEA can also act by inhibiting FAAH expression (Di Marzo et al, 2001b)which subsequently enhances AEA effects at CB or transient vanilloid 1 channel (TRPV1) receptors (De Petrocellis et al, 2001). PEA's anti-inflammatory effect also may be produced by its local antagonism or downregulation of mast cell degranulation (Jack, 1996;Mazzari et al, 1996;Re et al, 2007). Another possible mechanism by which PEA exerts its anti-edema effects is by activating peroxisome proliferator activated receptor-α (PPAR-α), as PEA lacks efficacy in models of edema in PPAR-α (-/-) mice (Lo Verme et al, 2005a).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of fatty acid amides in the carrageenan-induced paw edema model

et al. 2008

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While it has long been recognized that Δ 9 -tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis, and other cannabinoid receptor agonists possess anti-inflammatory properties, their well known CNS effects have dampened enthusiasm for therapeutic development. On the other hand, genetic deletion of fatty acid amide hydrolase (FAAH), the enzyme responsible for degradation of fatty acid amides, including endogenous cannabinoid N-arachidonoyl ethanolamine (anandamide; AEA), N-palmitoyl ethanolamine (PEA), N-oleoyl ethanolamine (OEA), and oleamide, also elicits anti-edema, but does not produce any apparent cannabinoid effects. The purpose of the present study was to investigate whether exogenous administration of FAAs would augment the anti-inflammatory phenotype of FAAH (-/-) mice in the carrageenan model. Thus, we evaluated the effects of the FAAs AEA, PEA, OEA, and oleamide in wild-type and FAAH (-/-) mice. For comparison, we evaluated the anti-edema effects of THC, dexamethasone (DEX), a synthetic glucocorticoid, diclofenac (DIC), a nonselective cyclooxygenase (COX) inhibitor, in both genotypes. A final study determined if tolerance to the anti-edema effects of PEA occurs after repeated dosing. PEA, THC, DEX, DIC elicited significant decreases in carrageenan-induced paw edema in wild type mice. In contrast OEA produced a less reliable anti-edema effect than these other drugs, and AEA and oleamide failed to produce any significant decreases in paw edema. Moreover, none of the agents evaluated augmented the anti-edema phenotype of FAAH (-/-) mice, suggesting that maximal antiedema effects had already been established. PEA was the most effective FAA in preventing paw edema and its effects did not undergo tolerance. While the present findings do not support a role for AEA in preventing carrageenan-induced edema, PEA administration and FAAH blockade elicited anti-edema effects of an equivalent magnitude as produced by THC, DEX, and DIC in this assay.

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“…With respect to inflammation and pain, Re et al (2007) authored a review in which they focused on the role of an endogenous fatty acid amide analogue of the endocannabinoid AEA -termed palmitoylethanolamide (PEA) -in tissue protection. PEA does not bind to CB 1 and CB 2 receptors but has affinity for the cannabinoid-like G-coupled receptors GPR55 and GPR119.…”

Section: The Use Of Cannabinoids In Animalsmentioning

confidence: 99%

“…It acts as a modulator of glia and mast cells (Keppel Hesselink 2012), and has been shown to enhance AEA activity through a so-called "entourage effect" (Mechoulam et al 1998). Re et al (2007) concluded that the use of natural compounds such as PEA influences endogenous protective mechanisms and can represent an advantageous and beneficial novel therapeutic approach in veterinary medicine. Regarding dermatology, Scarampella et al (2001) administered the substance PLR 120 (an analogue of PEA) to 15 cats with eosinophilic granulomas or eosinophilic plaques.…”

Section: The Use Of Cannabinoids In Animalsmentioning

confidence: 99%

The use of cannabinoids in animals and therapeutic implications for veterinary medicine: a review

Landa¹,

Šulcová²,

Gbelec³

2016

Vet. Med. - Czech

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Cannabinoids/medical marijuana and their possible therapeutic use have received increased attention in human medicine during the last years. This increased attention is also an issue for veterinarians because particularly companion animal owners now show an increased interest in the use of these compounds in veterinary medicine. This review sets out to comprehensively summarise well known facts concerning properties of cannabinoids, their mechanisms of action, role of cannabinoid receptors and their classification. It outlines the main pharmacological effects of cannabinoids in laboratory rodents and it also discusses examples of possible beneficial use in other animal species (ferrets, cats, dogs, monkeys) that have been reported in the scientific literature. Finally, the article deals with the prospective use of cannabinoids in veterinary medicine. We have not intended to review the topic of cannabinoids in an exhaustive manner; rather, our aim was to provide both the scientific community and clinical veterinarians with a brief, concise and understandable overview of the use of cannabinoids in veterinary medicine.

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Palmitoylethanolamide, endocannabinoids and related cannabimimetic compounds in protection against tissue inflammation and pain: Potential use in companion animals

Cited by 175 publications

References 88 publications

Dynamic changes to the endocannabinoid system in models of chronic pain

Dynamic changes to the endocannabinoid system in models of chronic pain

Evaluation of fatty acid amides in the carrageenan-induced paw edema model

The use of cannabinoids in animals and therapeutic implications for veterinary medicine: a review

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