The Interaction Between Intrathecal Administration of Low Doses of Palmitoylethanolamide and AM251 in Formalin-Induced Pain Related Behavior and Spinal Cord IL1-β Expression in Rats

Naderi, Nima; Majidi, Mohsen; Mousavi, Zahra; Tusi, Solaleh Khoramian; Mansouri, Zahra; Khodagholi, Fariba

doi:10.1007/s11064-011-0672-2

Cited by 19 publications

(10 citation statements)

References 28 publications

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“…The orphan receptor GPR55 has been proposed to mediate some of the pharmacological actions of CBs (Pertwee, ; Ryberg et al ., ; Naderi et al ., ). Similar to CB 1 and CB 2 receptors, GPR55 is expressed throughout the rodent gastrointestinal tract (Schicho et al ., ; Schicho and Storr, ).…”

Section: Discussionmentioning

confidence: 98%

Palmitoylethanolamide, a naturally occurring lipid, is an orally effective intestinal anti‐inflammatory agent

Borrelli

Romano

Petrosino

et al. 2014

British J Pharmacology

150

141

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BACKGROUND AND PURPOSEPalmitoylethanolamide (PEA) acts via several targets, including cannabinoid CB1 and CB2 receptors, transient receptor potential vanilloid type-1 (TRPV1) ion channels, peroxisome proliferator-activated receptor alpha (PPAR α) and orphan G protein-coupled receptor 55 (GRR55), all involved in the control of intestinal inflammation. Here, we investigated the effect of PEA in a murine model of colitis. EXPERIMENTAL APPROACHColitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Inflammation was assessed by evaluating inflammatory markers/parameters and by histology; intestinal permeability by a fluorescent method; colonic cell proliferation by immunohistochemistry; PEA and endocannabinoid levels by liquid chromatography mass spectrometry; receptor and enzyme mRNA expression by quantitative RT-PCR. KEY RESULTSDNBS administration caused inflammatory damage, increased colonic levels of PEA and endocannabinoids, down-regulation of mRNA for TRPV1 and GPR55 but no changes in mRNA for CB1, CB2 and PPARα. Exogenous PEA (i.p. and/or p.o., 1 mg·kg −1 ) attenuated inflammation and intestinal permeability, stimulated colonic cell proliferation, and increased colonic TRPV1 and CB1 receptor expression. The anti-inflammatory effect of PEA was attenuated or abolished by CB2 receptor, GPR55 or PPARα antagonists and further increased by the TRPV1 antagonist capsazepine. CONCLUSIONS AND IMPLICATIONSPEA improves murine experimental colitis, the effect being mediated by CB2 receptors, GPR55 and PPARα, and modulated by TRPV1 channels. Abbreviations2-AG, 2-arachidonoylglycerol; CB, cannabinoid; DNBS, 2,4,6-dinitrobenzenesulfonic acid; DSS, dextran sodium sulphate; FAAH, fatty acid amide hydrolase; GDE1, glycerophosphodiester PDE 1; IBD, inflammatory bowel disease; MPO, myeloperoxidase; NAAA, N-acylethanolamine-hydrolysing acid amidase; NAPE-PLD, N-arachidonyl-phosphatidylethanolamine PLD; OEA, oleoylethanolamide; PEA, palmitoylethanolamide; TRPV1, transient receptor potential vanilloid type-1

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Section: Discussionmentioning

confidence: 98%

Palmitoylethanolamide, a naturally occurring lipid, is an orally effective intestinal anti‐inflammatory agent

Borrelli

Romano

Petrosino

et al. 2014

British J Pharmacology

150

141

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“…Generally consistent with a potential analgesic role of GPR55 are also reports that intrathecal administration of AM251 or PEA (a CB1 antagonist and indirect-acting agonist, respectively, which both possess GPR55 agonist activity; e . g ., [8]), results in analgesia in the formalin test [29]. However, in contrast, Gpr55 KO mice were reported to lack the typical inflammatory mechanical hyperalgesia following intraplantar administration of Freund's complete adjuvant [20].…”

Section: Discussionmentioning

confidence: 99%

Deletion of Gpr55 Results in Subtle Effects on Energy Metabolism, Motor Activity and Thermal Pain Sensation

Bjursell

Ryberg

et al. 2016

PLoS ONE

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The G-protein coupled receptor 55 (GPR55) is activated by cannabinoids and non-cannabinoid molecules and has been speculated to play a modulatory role in a large variety of physiological and pathological processes, including in metabolically perturbed states. We therefore generated male mice deficient in the gene coding for the cannabinoid/lysophosphatidylinositol (LPI) receptor Gpr55 and characterized them under normal dietary conditions as well as during high energy dense diet feeding followed by challenge with the CB1 receptor antagonist/GPR55 agonist rimonabant. Gpr55 deficient male mice (Gpr55 KO) were phenotypically indistinguishable from their wild type (WT) siblings for the most part. However, Gpr55 KO animals displayed an intriguing nocturnal pattern of motor activity and energy expenditure (EE). During the initial 6 hours of the night, motor activity was significantly elevated without any significant effect observed in EE. Interestingly, during the last 6 hours of the night motor activity was similar but EE was significantly decreased in the Gpr55 KO mice. No significant difference in motor activity was detected during daytime, but EE was lower in the Gpr55 KO compared to WT mice. The aforementioned patterns were not associated with alterations in energy intake, daytime core body temperature, body weight (BW) or composition, although a non-significant tendency to increased adiposity was seen in Gpr55 KO compared to WT mice. Detailed analyses of daytime activity in the Open Field paradigm unveiled lower horizontal activity and rearing time for the Gpr55 KO mice. Moreover, the Gpr55 KO mice displayed significantly faster reaction time in the tail flick test, indicative of thermal hyperalgesia. The BW-decreasing effect of rimonabant in mice on long-term cafeteria diet did not differ between Gpr55 KO and WT mice. In conclusion, Gpr55 deficiency is associated with subtle effects on diurnal/nocturnal EE and motor activity behaviours but does not appear per se critically required for overall metabolism or behaviours.

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“…This receptor is a regulator of gene networks which control pain and inflammation5, probably by switching off the nuclear factor-kappaB signaling cascade,4–7 a key element in the transcription of genes for proinflammatory mediators (cytokine, chemokines, nitric oxide). PEA also has affinity to cannabinoid-like G protein-coupled receptors GPR55 and GPR119 8. PEA can influence ion channels (eg, potassium channels) that play a role in pain 9.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions: a case series

Hesselink

Hekker²

2012

JPR

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The Interaction Between Intrathecal Administration of Low Doses of Palmitoylethanolamide and AM251 in Formalin-Induced Pain Related Behavior and Spinal Cord IL1-β Expression in Rats

Cited by 19 publications

References 28 publications

Palmitoylethanolamide, a naturally occurring lipid, is an orally effective intestinal anti‐inflammatory agent

Palmitoylethanolamide, a naturally occurring lipid, is an orally effective intestinal anti‐inflammatory agent

Deletion of Gpr55 Results in Subtle Effects on Energy Metabolism, Motor Activity and Thermal Pain Sensation

Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions: a case series

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