title: Metoclopramide inhibits trigeminovascular activation:evidence for effective acute attack treatment in migraine.
abstract: Metoclopramide is an effective and commonly used medication in acute migraine treatment but an experimental evidence base is lacking. We aimed to investigate the antimigraine effect of metoclopramide in a migraine model and whether the analgesic effect of metoclopramide was likely to be D2receptor-mediated.
  
  
  
  Cortical spreading depression (CSD) was used to model migraine in adult male Wistar rats. Five CSDs were induced by pinprick. Metoclopramide (two different doses), raclopride, or 0.9% saline were administered 30 min before CSD induction. Two hours after the experiments, brain tissues were examined for c-fos activation.
  
  
  
  In metoclopramide groups brain stem c-fos expression was significantly lower than in the CSD side of the saline group (P = 0.002). In the raclopride group, ipsilateral brain stem c-fos expression was also lower than in the saline group (P = 0.002). No difference in c-fos expression in the ipsilateral trigeminal nucleus caudalis between the raclopride and metoclopramide groups was observed (P > 0.05).
  
  
  
  Metoclopramide is shown to suppress trigeminovascular activation for the first time, providing an experimental basis for its role in migraine. The analgesic effect of metoclopramide is likely to be mediated by D2receptors since raclopride, a selective D2receptor antagonist, suppresses trigeminovascular activation similarly.
authors.affiliation: Neuropsychiatry Center, Faculty of Medicine, Gazi University, Ankara, Turkey.
authors.forename: Hacer
authors.initials: H
authors.lastname: Doğanay Aydin
authors.affiliation: Neuropsychiatry Center, Faculty of Medicine, Gazi University, Ankara, Turkey.
authors.forename: Doğa
authors.initials: D
authors.lastname: Vuralli
authors.affiliation: Department of Anesthesiology and Reanimation, Faculty of Medicine, Gazi University, Ankara, Turkey.
authors.forename: Didem Tuba
authors.initials: DT
authors.lastname: Akçali
authors.affiliation: Neuropsychiatry Center, Faculty of Medicine, Gazi University, Ankara, Turkey.
authors.forename: Hayrunnisa
authors.initials: H
authors.lastname: Bolay
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D013181:Cortical Spreading Depression / Q000187:drug effects; D004195:Disease Models, Animal; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D008881:Migraine Disorders / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000378:metabolism; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects*
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D020891:Raclopride; D008787:Metoclopramide