title: Effects of peripheral FAAH blockade on NTG-induced hyperalgesia--evaluation of URB937 in an animal model of migraine.
abstract: BACKGROUND
  Systemic nitroglycerin (NTG) activates brain nuclei involved in nociceptive transmission as well as in neuroendocrine and autonomic functions in rats. These changes are considered relevant for migraine because NTG consistently provokes spontaneous-like migraine attacks in migraineurs. Several studies have suggested a relationship between the endocannabinoid levels and pain mediation in migraine. URB937, a peripheral inhibitor of fatty acid amide hydrolase (FAAH)-the enzyme that degrades anandamide, produces analgesia in animal models of pain, but there is no information on its effects in migraine.
  
  
  OBJECTIVE
  We evaluated whether URB937 alters nociceptive responses in the animal model of migraine based on NTG administration in male rats, using the tail flick test and the plantar and orofacial formalin tests, under baseline conditions and after NTG administration. Furthermore, we investigated whether URB937 affects NTG-induced c-Fos expression in the brain.
  
  
  RESULTS
  During the tail flick test, URB937 showed an antinociceptive effect in baseline conditions and it blocked NTG-induced hyperalgesia. URB937 also proved effective in counteracting NTG-induced hyperalgesia during both the plantar and orofacial formalin tests. Mapping of brain nuclei activated by NTG indicates that URB937 significantly reduces c-Fos expression in the nucleus trigeminalis caudalis and the locus coeruleus.
  
  
  CONCLUSIONS
  The data suggest that URB937 is capable of changing, probably via indirect mechanisms, the functional status of central structures that are important for pain transmission in an animal model of migraine.
authors.affiliation: Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Centre, C. Mondino National Neurological Institute, Italy rosaria.greco@mondino.it.
authors.forename: R
authors.initials: R
authors.lastname: Greco
authors.affiliation: Dept. of Drug Discovery and Development, Istituto Italiano di Tecnologia, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Bandiera
authors.affiliation: Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Centre, C. Mondino National Neurological Institute, Italy.
authors.forename: A S
authors.initials: AS
authors.lastname: Mangione
authors.affiliation: Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Centre, C. Mondino National Neurological Institute, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Demartini
authors.affiliation: Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseases, National Neurological Institute "C. Mondino," Italy.
authors.forename: F
authors.initials: F
authors.lastname: Siani
authors.affiliation: Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Centre, C. Mondino National Neurological Institute, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Nappi
authors.affiliation: Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Centre, C. Mondino National Neurological Institute, Italy Dept. of Brain and Behavioural Sciences, University of Pavia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Sandrini
authors.affiliation: Dept. of Drug Discovery and Development, Istituto Italiano di Tecnologia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Guijarro
authors.affiliation: Dept. of Drug Discovery and Development, Istituto Italiano di Tecnologia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Armirotti
authors.affiliation: Dept. of Drug Discovery and Development, Istituto Italiano di Tecnologia, Italy Dept. of Anatomy and Neurobiology, University of California, USA.
authors.forename: D
authors.initials: D
authors.lastname: Piomelli
authors.affiliation: Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Centre, C. Mondino National Neurological Institute, Italy Dept. of Brain and Behavioural Sciences, University of Pavia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Tassorelli
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000700:Analgesics / Q000008:administration & dosage; D000818:Animals; D002186:Cannabinoids / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control*; D008297:Male; D005996:Nitroglycerin; D058748:Pain Perception / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D000700:Analgesics; D002186:Cannabinoids; D005996:Nitroglycerin; D000099252:Fatty Acid Amide Hydrolases; C552918:URB937
keywords: Migraine; URB937; anandamide; hyperalgesia; nitroglycerin