title: Activation of meningeal nociceptors by cortical spreading depression: implications for migraine with aura.
abstract: Attacks of migraine with aura represent a phenomenon in which abnormal neuronal activity in the cortex produces sensory disturbances (aura) some 20-40 min before the onset of headache. The purpose of this study was to determine whether cortical spreading depression (CSD)--an event believed to underlie visual aura--can give rise to activation of nociceptors that innervate the meninges--an event believed to set off migraine headache. CSD was induced in anesthetized male rats by stimulation of the visual cortex with electrical pulses, pin prick, or KCl; single-unit activity of meningeal nociceptors was monitored in vivo in the rat before and after CSD. Regardless of the method of cortical stimulation, induction of CSD was recorded in 64 trials. In 31 of those trials, CSD induced a twofold increase in meningeal nociceptor firing rate that persisted for 37.0 +/- 4.6 min in trials in which activity returned to baseline, or >68 min in trials in which activity remained heightened at the time recording was interrupted. In two-thirds of the trials, onset of long-lasting neuronal activation began approximately 14 min after the wave of CSD. The findings demonstrates for the first time that induction of CSD by focal stimulation of the rat visual cortex can lead to long-lasting activation of nociceptors that innervate the meninges. We suggest that migraine with aura is initiated by waves of CSD that lead up to delayed activation of the trigeminovascular pathway.
authors.affiliation: Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center, and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Xichun
authors.initials: X
authors.lastname: Zhang
authors.forename: Dan
authors.initials: D
authors.lastname: Levy
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Noseda
authors.forename: Vanessa
authors.initials: V
authors.lastname: Kainz
authors.forename: Moshe
authors.initials: M
authors.lastname: Jakubowski
authors.forename: Rami
authors.initials: R
authors.lastname: Burstein
mesh_terms: D000200:Action Potentials; D000818:Animals; D013181:Cortical Spreading Depression / Q000502:physiology*; D004558:Electric Stimulation; D008297:Male; D008578:Meninges / Q000502:physiology* / Q000503:physiopathology; D020325:Migraine with Aura / Q000503:physiopathology; D009498:Neurotoxins / Q000633:toxicity; D009619:Nociceptors / Q000502:physiology*; D010812:Physical Stimulation; D011189:Potassium Chloride / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014793:Visual Cortex / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology
chemical_list: D009498:Neurotoxins; D011189:Potassium Chloride