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Dual Inhibition of FAAH and MAGL Counteracts Migraine-like Pain and Behavior in an Animal Model of Migraine

The endocannabinoid system exerts an important role in pain processing and modulation. Modulation of the system with hydrolase inhibitors of anandamide (AEA) or 2-arachidonyl glycerol (2-AG) has proved effective in reducing migraine-like features in animal models of migraine. Here, we investigated t...

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Autores principales: Greco, Rosaria, Demartini, Chiara, Francavilla, Miriam, Zanaboni, Anna Maria, Tassorelli, Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534238/
https://www.ncbi.nlm.nih.gov/pubmed/34685523
http://dx.doi.org/10.3390/cells10102543
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author Greco, Rosaria
Demartini, Chiara
Francavilla, Miriam
Zanaboni, Anna Maria
Tassorelli, Cristina
author_facet Greco, Rosaria
Demartini, Chiara
Francavilla, Miriam
Zanaboni, Anna Maria
Tassorelli, Cristina
author_sort Greco, Rosaria
collection PubMed
description The endocannabinoid system exerts an important role in pain processing and modulation. Modulation of the system with hydrolase inhibitors of anandamide (AEA) or 2-arachidonyl glycerol (2-AG) has proved effective in reducing migraine-like features in animal models of migraine. Here, we investigated the effect of dual inhibition of the AEA and 2-AG catabolic pathways in the nitroglycerin-based animal model of migraine. The dual inhibitor JZL195 was administered to rats 2 h after nitroglycerin or vehicle injection. Rats were then exposed to the open field test and the orofacial formalin test. At the end of the tests, they were sacrificed to evaluate calcitonin gene-related peptide (CGRP) serum levels and gene expression of CGRP and cytokines in the cervical spinal cord and the trigeminal ganglion. The dual inhibitor significantly reduced the nitroglycerin-induced trigeminal hyperalgesia and pain-associated behavior, possibly via cannabinoid 1 receptors-mediated action, but it did not change the hypomotility and the anxiety behaviors induced by nitroglycerin. The decreased hyperalgesia was associated with a reduction in CGRP and cytokine gene expression levels in central and peripheral structures and reduced CGRP serum levels. These data suggest an antinociceptive synergy of the endocannabinoid action in peripheral and central sites, confirming that this system participates in reduction of cephalic pain signals.
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spelling pubmed-85342382021-10-23 Dual Inhibition of FAAH and MAGL Counteracts Migraine-like Pain and Behavior in an Animal Model of Migraine Greco, Rosaria Demartini, Chiara Francavilla, Miriam Zanaboni, Anna Maria Tassorelli, Cristina Cells Article The endocannabinoid system exerts an important role in pain processing and modulation. Modulation of the system with hydrolase inhibitors of anandamide (AEA) or 2-arachidonyl glycerol (2-AG) has proved effective in reducing migraine-like features in animal models of migraine. Here, we investigated the effect of dual inhibition of the AEA and 2-AG catabolic pathways in the nitroglycerin-based animal model of migraine. The dual inhibitor JZL195 was administered to rats 2 h after nitroglycerin or vehicle injection. Rats were then exposed to the open field test and the orofacial formalin test. At the end of the tests, they were sacrificed to evaluate calcitonin gene-related peptide (CGRP) serum levels and gene expression of CGRP and cytokines in the cervical spinal cord and the trigeminal ganglion. The dual inhibitor significantly reduced the nitroglycerin-induced trigeminal hyperalgesia and pain-associated behavior, possibly via cannabinoid 1 receptors-mediated action, but it did not change the hypomotility and the anxiety behaviors induced by nitroglycerin. The decreased hyperalgesia was associated with a reduction in CGRP and cytokine gene expression levels in central and peripheral structures and reduced CGRP serum levels. These data suggest an antinociceptive synergy of the endocannabinoid action in peripheral and central sites, confirming that this system participates in reduction of cephalic pain signals. MDPI 2021-09-26 /pmc/articles/PMC8534238/ /pubmed/34685523 http://dx.doi.org/10.3390/cells10102543 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Greco, Rosaria
Demartini, Chiara
Francavilla, Miriam
Zanaboni, Anna Maria
Tassorelli, Cristina
Dual Inhibition of FAAH and MAGL Counteracts Migraine-like Pain and Behavior in an Animal Model of Migraine
title Dual Inhibition of FAAH and MAGL Counteracts Migraine-like Pain and Behavior in an Animal Model of Migraine
title_full Dual Inhibition of FAAH and MAGL Counteracts Migraine-like Pain and Behavior in an Animal Model of Migraine
title_fullStr Dual Inhibition of FAAH and MAGL Counteracts Migraine-like Pain and Behavior in an Animal Model of Migraine
title_full_unstemmed Dual Inhibition of FAAH and MAGL Counteracts Migraine-like Pain and Behavior in an Animal Model of Migraine
title_short Dual Inhibition of FAAH and MAGL Counteracts Migraine-like Pain and Behavior in an Animal Model of Migraine
title_sort dual inhibition of faah and magl counteracts migraine-like pain and behavior in an animal model of migraine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534238/
https://www.ncbi.nlm.nih.gov/pubmed/34685523
http://dx.doi.org/10.3390/cells10102543
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