title: Utility of different outcome measures for the nitroglycerin model of migraine in mice.
abstract: BACKGROUND
  Majority of the work for establishing nitroglycerin (NTG)-induced migraine models in animals was done in rats, though recently some studies in mice were also reported. Different special formulations of NTG were investigated in various studies; however, NTG treated groups were often compared to simple saline treated control groups. The aim of the present studies was to critically assess the utility of a panel of potential outcome measures in mice by revisiting previous findings and investigating endpoints that have not been tested in mice yet.
  
  
  METHODS
  We investigated two NTG formulations, Nitrolingual and Nitro Pohl, at an intraperitoneal dose of 10mg/kg, in comparison with relevant vehicle controls, and evaluated the following outcome measures: light aversive behaviour, cranial blood perfusion by laser Doppler imaging, number of c-Fos- and neuronal nitrogen monoxide synthase (nNOS)-immunoreactive neurons in the trigeminal nucleus caudalis (TNC) and trigeminal ganglia, thermal hyperalgesia and tactile allodynia of the hind paw and orofacial pain hypersensitivity.
  
  
  RESULTS
  We could not confirm previous reports of significant NTG-induced changes in light aversion and cranial blood perfusion of mice but we observed considerable effects elicited by the vehicle of Nitrolingual. In contrast, the vehicle of Nitro Pohl was apparently inert. Increased c-Fos expression in the TNC, thermal hyperalgesia, tactile allodynia and orofacial hypersensitivity were apparently good endpoints in mice that were increased by NTG-administration. The NTG-induced increase in c-Fos expression was prevented by topiramate but not by sumatriptan treatment. However, the NTG-induced orofacial hypersensitivity was dose dependently attenuated by sumatriptan.
  
  
  CONCLUSIONS
  Our results pointed to utilisable NTG formulations and outcome measures for NTG-induced migraine models in mice. Pending further cross-validation with positive and negative control drugs in these mouse models and in the human NTG models of migraine, these tests might be valuable translational research tools for development of new anti-migraine drugs.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Szigeti u. 12, H-7624 Pécs, Hungary; Research Division, Gedeon Richter Plc., H-1103 Budapest, Gyömrői út 19-21, Hungary. Electronic address: farkass1@gmail.com.
authors.forename: Sándor
authors.initials: S
authors.lastname: Farkas
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Szigeti u. 12, H-7624 Pécs, Hungary; János Szentágothai Research Centre, University of Pécs, Ifjúság út 20, H-7624 Pécs, Hungary. Electronic address: kata.bolcskei@aok.pte.hu.
authors.forename: Kata
authors.initials: K
authors.lastname: Bölcskei
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Szigeti u. 12, H-7624 Pécs, Hungary; János Szentágothai Research Centre, University of Pécs, Ifjúság út 20, H-7624 Pécs, Hungary. Electronic address: adri.markovics@gmail.com.
authors.forename: Adrienn
authors.initials: A
authors.lastname: Markovics
authors.affiliation: Laboratory of Neuropharmacology, Pharmacological and Drug Safety Research, Gedeon Richter Plc., H-1103 Budapest, Gyömrői út 19-21, Hungary. Electronic address: anivarga@richter.hu.
authors.forename: Anita
authors.initials: A
authors.lastname: Varga
authors.affiliation: Laboratory of Neuropharmacology, Pharmacological and Drug Safety Research, Gedeon Richter Plc., H-1103 Budapest, Gyömrői út 19-21, Hungary. Electronic address: i.kisvarga@richter.hu.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Kis-Varga
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Szigeti u. 12, H-7624 Pécs, Hungary. Electronic address: viktoria.kormos@gmail.com.
authors.forename: Viktória
authors.initials: V
authors.lastname: Kormos
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of Pécs, Szigeti u. 12, H-7624 Pécs, Hungary. Electronic address: balazs.b.gaszner@aok.pte.hu.
authors.forename: Balázs
authors.initials: B
authors.lastname: Gaszner
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Szigeti u. 12, H-7624 Pécs, Hungary; Laboratory of Neuropharmacology, Pharmacological and Drug Safety Research, Gedeon Richter Plc., H-1103 Budapest, Gyömrői út 19-21, Hungary. Electronic address: horvathcsiti@gmail.com.
authors.forename: Csilla
authors.initials: C
authors.lastname: Horváth
authors.affiliation: Neurology Department, University of Szeged, Faculty of Medicine, H-6725 Szeged, Semmelweis u. 6, Hungary; MTA-SZTE Neuroscience Research Group, H-6725 Szeged, Semmelweis u. 6, Hungary. Electronic address: tukabernadett@googlemail.com.
authors.forename: Bernadett
authors.initials: B
authors.lastname: Tuka
authors.affiliation: Neurology Department, University of Szeged, Faculty of Medicine, H-6725 Szeged, Semmelweis u. 6, Hungary. Electronic address: tajti.janos@med.u-szeged.hu.
authors.forename: János
authors.initials: J
authors.lastname: Tajti
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Szigeti u. 12, H-7624 Pécs, Hungary; János Szentágothai Research Centre, University of Pécs, Ifjúság út 20, H-7624 Pécs, Hungary; MTA-PTE NAP B Chronic Pain Research Group, Faculty of Medicine, University of Pécs, Szigeti u. 12, H-7624 Pécs, Hungary. Electronic address: zsuzsanna.helyes@aok.pte.hu.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Helyes
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051379:Mice; D008881:Migraine Disorders / Q000188:drug therapy* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology*; D017063:Outcome Assessment, Health Care; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D014278:Trigeminal Nuclei / Q000187:drug effects / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D014665:Vasodilator Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D005996:Nitroglycerin
keywords: Cranial blood flow; Light aversion; Methods; Migraine; Nitroglycerin; Orofacial allodynia; Thermal hyperalgesia; Trigeminovascular system; c-Fos; nNOS