title: Cortical spreading depression decreases Fos expression in rat periaqueductal gray matter.
abstract: The migraine headache involves activation and central sensitization of the trigeminovascular pain pathway. The migraine aura is likely due to cortical spreading depression (CSD), a propagating wave of brief neuronal depolarization followed by prolonged inhibition. The precise link between CSD and headache remains controversial. Our objectives were to study the effect of CSD on neuronal activation in the periaqueductal grey matter (PAG), an area known to control pain and autonomic functions, and to be involved in migraine pathogenesis. Fos-immunoreactive nuclei were counted in rostral PAG and Edinger-Westphal nuclei (PAG-EWn bregma -6.5 mm), and caudal PAG (bregma -8 mm) of 17 adult male Sprague-Dawley rats after KCl-induced CSD under chloral hydrate anesthesia. Being part of a pharmacological study, six animals had received, for the preceding 4 weeks daily, intraperitoneal injections of lamotrigine (15 mg/kg), six others had been treated with saline, while five sham-operated animals served as controls. We found that the number of Fos-immunoreactive nuclei in the PAG decreased after CSD provocation. There was no difference between lamotrigine- and saline-treated animals. The number of CSDs correlated negatively with Fos-immunoreactive counts. CSD-linked inhibition of neuronal activity in the PAG might play a role in central sensitization during migraine attacks and contribute to a better understanding of the link between the aura and the headache.
authors.affiliation: Giga-Neurosciences, Headache Research Unit, University of Liege, Liege 4000, Belgium; Taras Shevchenko National University of Kyiv, Volodymyrska Str. 64, Kyiv 01033, Ukraine; INRA, Nutrition et Neurobiologie Intégrée and University Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 146 Rue Léo-Saignat, Bordeaux Cedex 33076, France. Electronic address: vlabogd@yahoo.com.
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Borysovych Bogdanov
authors.affiliation: Taras Shevchenko National University of Kyiv, Volodymyrska Str. 64, Kyiv 01033, Ukraine.
authors.forename: Olena Viktorivna
authors.initials: OV
authors.lastname: Bogdanova
authors.affiliation: Giga-Neurosciences, Headache Research Unit, University of Liege, Liege 4000, Belgium.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Lombard
authors.affiliation: Giga-Neurosciences, Headache Research Unit, University of Liege, Liege 4000, Belgium.
authors.forename: Virginie
authors.initials: V
authors.lastname: Chauvel
authors.affiliation: Giga-Neurosciences, Headache Research Unit, University of Liege, Liege 4000, Belgium.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Multon
authors.affiliation: Taras Shevchenko National University of Kyiv, Volodymyrska Str. 64, Kyiv 01033, Ukraine.
authors.forename: Larysa Ivanivna
authors.initials: LI
authors.lastname: Kot
authors.affiliation: Taras Shevchenko National University of Kyiv, Volodymyrska Str. 64, Kyiv 01033, Ukraine.
authors.forename: Mykola Yukhymovych
authors.initials: MY
authors.lastname: Makarchuk
authors.affiliation: Giga-Neurosciences, Headache Research Unit, University of Liege, Liege 4000, Belgium.
authors.forename: Jean
authors.initials: J
authors.lastname: Schoenen
mesh_terms: D000818:Animals; D002452:Cell Count; D013181:Cortical Spreading Depression; D065839:Edinger-Westphal Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D000077213:Lamotrigine; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010487:Periaqueductal Gray / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D014227:Triazines / Q000494:pharmacology
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D014227:Triazines; D000077213:Lamotrigine
keywords: Cortical spreading depression; Edinger–Westphal nucleus; Fos expression; Migraine; Periaqueductal gray matter