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The Journal of Headache and Pain

Official Journal of the "European Headache Federation" and of "Lifting The Burden - The Global Campaign against Headache"

The Journal of Headache and Pain Cover Image

Volume 16 Supplement 1

1st Joint ANIRCEF-SISC Congress

Open Access

P007. Inhibition of monoacylglycerol lipase activity modulates the activation of brain structures relevant for migraine pathogenesis

  • Rosaria Greco1,
  • Tiziano Bandiera2,
  • Antonina S Mangione1,
  • Chiara Demartini1,
  • Giuseppe Nappi1,
  • Giorgio Sandrini1,
  • Daniele Piomelli2 and
  • Cristina Tassorelli1, 3Email author
The Journal of Headache and Pain201516(Suppl 1):A165

Published: 28 September 2015


MigraineMigraine AttackNucleus TrigeminalisMigraine PainNucleus Trigeminalis Caudalis


Experimental evidence shows that the anti-nociceptive action of endocannabinoids, related to the modulation of the trigeminovascular system activity, may be helpful for prompting new targets for the treatment of migraine. URB602 is an inhibitor of monoacylglycerol lipase (MAGL), a key enzyme in the hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG). URB602 induces analgesia in animal pain models not related to migraine, but there is no pre-clinical information as regards to its potential effect in migraine pain.


To evaluate whether URB602 administration interferes with the level of activation of brain structures involved in migraine.


Nitroglycerin (NTG) induces neuronal activation in a specific subset of brain nuclei that are considered relevant for the development of migraine attacks. In this study we evaluated the changes caused by URB602 in NTG-induced neuronal activation. Male Sprague Dawley rats were treated with NTG (10mg/kg, i.p.) followed by URB602 (2mg/kg, i.p.) or vehicle (DMSO, 1ml/kg, i.p.). Their brains were processed for the detection of c-Fos protein, used as an indicator of brain activation.


URB602 alone did not change Fos expression in the brain nuclei under evaluation. When administered 3 hours after NTG, URB602 reduced NTG-induced Fos expression in all the cerebral areas that were examined, with a significant effect in nucleus trigeminalis caudalis and ventrolateral column of periaqueductal grey.


The inhibition of MAGL activity, with the theoretical increase of central content of 2-AG, may modulate the activation of structures involved in pain perception and pain integration in an animal model specific for migraine.



This study was supported by a grant from the Italian Ministry of Health to “C. Mondino” National Neurological Institute (Ricerca Corrente 2013).

Authors’ Affiliations

Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Centre, “C. Mondino” National Neurological Institute, Pavia, Italy
Drug Discovery and Development Department, Fondazione Istituto Italiano di Tecnologia, Genova, Italy
Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy


© Greco et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.


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