title: A naturalistic glyceryl trinitrate infusion migraine model in the rat.
abstract: OBJECTIVE
  Glyceryl trinitrate (GTN) infusion is a reliable method to provoke migraine-like headaches in humans. Previous studies have simulated this human model in anaesthetized or in awake rodents using GTN doses 10,000 times higher than used in humans. The relevance of such toxicological doses to migraine is not certain. Anaesthesia and low blood pressure caused by high GTN doses both can affect the expression of nociceptive marker c-fos. Therefore, our aim was to simulate the human GTN migraine model in awake rats using a clinically relevant dose.
  
  
  METHODS
  Awake rats were infused with GTN (4 µg/kg/min, for 20 min, i.v.), a dose just 8 times higher than in humans. mRNA and protein expression for c-fos were analysed in the trigeminal vascular system at various time points using RT-PCR and immunohistochemistry, respectively.
  
  
  RESULTS
  A significant upregulation of c-fos mRNA was observed in the trigeminal nucleus caudalis at 30 min and 2 h that was followed by an upregulation of Fos protein in the trigeminal nucleus caudalis at 2 h and 4 h after GTN infusion. Pre-treatment with sumatriptan attenuated the activation of Fos at 4 h, demonstrating the specificity of this model for migraine.
  
  
  CONCLUSIONS
  We present a validated naturalistic rat model suitable for screening of acute anti-migraine drugs.
authors.affiliation: University of Copenhagen, Denmark.
authors.forename: Roshni
authors.initials: R
authors.lastname: Ramachandran
authors.forename: Deepak Kumar
authors.initials: DK
authors.lastname: Bhatt
authors.forename: Kenneth Beri
authors.initials: KB
authors.lastname: Ploug
authors.forename: Jes
authors.initials: J
authors.lastname: Olesen
authors.forename: Inger
authors.initials: I
authors.lastname: Jansen-Olesen
authors.forename: Anders
authors.initials: A
authors.lastname: Hay-Schmidt
authors.forename: Saurabh
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000139:chemically induced* / Q000503:physiopathology; D005996:Nitroglycerin / Q000633:toxicity*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000633:toxicity*; D014851:Wakefulness
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D014665:Vasodilator Agents; D005996:Nitroglycerin