title: The modulatory effect of anandamide on nitroglycerin-induced sensitization in the trigeminal system of the rat.
abstract: BACKGROUND
  One of the human and animal models of migraine is the systemic administration of the nitric oxide donor (NO) nitroglycerin (NTG). NO can provoke migraine-like attacks in migraineurs and initiates a self-amplifying process in the trigeminal system, probably leading to central sensitization. Recent studies suggest that the endocannabinoid system is involved in nociceptive signal processing and cannabinoid receptor (CB) agonists are able to attenuate nociception in animal models of pain.
  
  
  OBJECTIVE
  The purpose of the present study was to investigate the modulatory effects of a CB agonist anandamide (AEA) on the NTG-induced expression of transient receptor potential vanilloid type 1 (TRPV1), neuronal nitric oxide synthase (nNOS), nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2) and kynurenine aminotransferase-II (KAT-II) in the upper cervical spinal cord (C1-C2) of the rat, where most of the trigeminal nociceptive afferents convey.
  
  
  METHODS
  A half hour before and one hour after NTG (10 mg/kg) or placebo injection, adult male Sprague-Dawley rats (n = 44) were treated with AEA (2 × 5 mg/kg). Four hours after placebo/NTG injection, the animals were perfused and the cervical spinal cords were removed for immunohistochemistry and Western blotting.
  
  
  CONCLUSIONS
  Our results show that NTG is able to increase TRPV1, nNOS, NF-κB and COX-2 and decrease KAT-II expression in the C1-C2 segments. On the other hand, we have found that AEA modulates the NTG-induced changes, thus it influences the activation and central sensitization process in the trigeminal system, probably via CBs.
authors.affiliation: Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Nagy-Grócz
authors.affiliation: Department of Neurology, University of Ulm, Germany.
authors.forename: Lilla
authors.initials: L
authors.lastname: Tar
authors.affiliation: MTA-SZTE Neuroscience Research Group, University of Szeged, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Bohár
authors.affiliation: Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Hungary.
authors.forename: Annamária
authors.initials: A
authors.lastname: Fejes-Szabó
authors.affiliation: Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Hungary.
authors.forename: Klaudia Flóra
authors.initials: KF
authors.lastname: Laborc
authors.affiliation: Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Hungary.
authors.forename: Eleonóra
authors.initials: E
authors.lastname: Spekker
authors.affiliation: Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Hungary MTA-SZTE Neuroscience Research Group, University of Szeged, Hungary vecsei.laszlo@med.u-szeged.hu.
authors.forename: László
authors.initials: L
authors.lastname: Vécsei
authors.affiliation: Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Hungary.
authors.forename: Árpád
authors.initials: Á
authors.lastname: Párdutz
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D015153:Blotting, Western; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D059333:Central Nervous System Sensitization / Q000187:drug effects*; D002574:Cervical Vertebrae; D004195:Disease Models, Animal; D063388:Endocannabinoids / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D008881:Migraine Disorders / Q000139:chemically induced / Q000503:physiopathology*; D020030:Nitric Oxide Donors / Q000633:toxicity; D005996:Nitroglycerin / Q000633:toxicity; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014276:Trigeminal Nerve / Q000187:drug effects*
chemical_list: D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D063388:Endocannabinoids; D020030:Nitric Oxide Donors; D053284:Polyunsaturated Alkamides; D005996:Nitroglycerin; C078814:anandamide
keywords: COX-2; KAT-II; Migraine; NF-κB; TRPV1; anandamide; nNOS; nitroglycerin; trigeminal system