Endocannabinoidomics: “Omics” Approaches Applied to Endocannabinoids and Endocannabinoid-Like Mediators

Piscitelli, Fabiana

doi:10.1016/b978-0-12-420126-2.00009-2

Cited by 4 publications

(1 citation statement)

References 62 publications

(51 reference statements)

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“…It has been repeatedly found in dozens of vegetable and animal food sources (in nanogram per gram level), from soy to carrots and from eggs to beef [ 39 , 46 ]. Moreover, PEA levels have also been detected in virtually any tissue and body fluid [ 46 , 51 ], where it is enzymatically produced “on demand” in response to actual or potential damage and enzymatically cleaved when it has served its purpose [ 51 , 52 , 113 , 114 , 115 ].…”

Section: Endogenous Pea and Pain Modulationmentioning

confidence: 99%

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

Rocca

Gamba²

2021

Animals

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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.

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Section: Endogenous Pea and Pain Modulationmentioning

confidence: 99%

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

Rocca

Gamba²

2021

Animals

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New approaches and challenges to targeting the endocannabinoid system

Marzo

2018

Nat Rev Drug Discov

360

381

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The endocannabinoid signalling system was discovered because receptors in this system are the targets of compounds present in psychotropic preparations of Cannabis sativa. The search for new therapeutics that target endocannabinoid signalling is both challenging and potentially rewarding, as endocannabinoids are implicated in numerous physiological and pathological processes. Hundreds of mediators chemically related to the endocannabinoids, often with similar metabolic pathways but different targets, have complicated the development of inhibitors of endocannabinoid metabolic enzymes but have also stimulated the rational design of multi-target drugs. Meanwhile, drugs based on botanical cannabinoids have come to the clinical forefront, synthetic agonists designed to bind cannabinoid receptor 1 with very high affinity have become a societal threat and the gut microbiome has been found to signal in part through the endocannabinoid network. The current development of drugs that alter endocannabinoid signalling and how this complex system could be pharmacologically manipulated in the future are described in this Opinion article.

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Genetic deletion of monoacylglycerol lipase leads to impaired cannabinoid receptor CB₁R signaling and anxiety‐like behavior

Imperatore

Morello

Luongo

et al. 2015

Journal of Neurochemistry

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Endocannabinoids (eCB) are key regulators of excitatory/ inhibitory neurotransmission at cannabinoid-1-receptor (CB 1 R)-expressing axon terminals. The most abundant eCB in the brain, that is 2-arachidonoylglycerol (2-AG), is hydrolyzed by the enzyme monoacylglycerol lipase (MAGL), whose chronic inhibition in the brain was reported to cause CB 1 R desensitization. We employed the MAGL knock-out mouse (MAGLÀ/À), a genetic model of congenital and sustained elevation of 2-AG levels in the brain, to provide morphological and biochemical evidence for b-arrestin2-mediated CB 1 R desensitization in brain regions involved in the control of emotional states, that is, the prefrontal cortex (PFC), amygdala, hippocampus and cerebellar cortex. We found a widespread CB 1 R/b-arrestin2 co-expression in the mPFC, amygdala and hippocampus accompanied by impairment of extracellular signal-regulated kinase signaling and elevation of vesicular glutamate transporter (VGluT1) at CB 1 R-positive excitatory terminals in the mPFC, or vesicular GABA transporter (VGAT) at CB 1 R-positive inhibitory terminals in the amygdala and hippocampus. The impairment of CB 1 R signaling in MAGLÀ/À mice was also accompanied by enhanced excitatory drive in the basolateral amygdala (BLA)-mPFC circuit, with subsequent elevation of glutamate release to the mPFC and anxiety-like and obsessive-compulsive behaviors, as assessed by the light/dark box and marble burying tests, respectively. Collectively, these data provide evidence for a barrestin2-mediated desensitization of CB 1 R in MAGLÀ/À mice, with impact on the synaptic plasticity of brain circuits involved in emotional functions.

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Endocannabinoidomics: “Omics” Approaches Applied to Endocannabinoids and Endocannabinoid-Like Mediators

Cited by 4 publications

References 62 publications

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

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

New approaches and challenges to targeting the endocannabinoid system

Genetic deletion of monoacylglycerol lipase leads to impaired cannabinoid receptor CB₁R signaling and anxiety‐like behavior

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Endocannabinoidomics: “Omics” Approaches Applied to Endocannabinoids and Endocannabinoid-Like Mediators

Cited by 4 publications

References 62 publications

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

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

New approaches and challenges to targeting the endocannabinoid system

Genetic deletion of monoacylglycerol lipase leads to impaired cannabinoid receptor CB1R signaling and anxiety‐like behavior

Contact Info

Product

Resources

About

Genetic deletion of monoacylglycerol lipase leads to impaired cannabinoid receptor CB₁R signaling and anxiety‐like behavior