RT Journal Article
SR Electronic
T1 Activation of Meningeal Nociceptors by Cortical Spreading Depression: Implications for Migraine with Aura
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8807
OP 8814
DO 10.1523/JNEUROSCI.0511-10.2010
VO 30
IS 26
A1 XiChun Zhang
A1 Dan Levy
A1 Rodrigo Noseda
A1 Vanessa Kainz
A1 Moshe Jakubowski
A1 Rami Burstein
YR 2010
UL http://www.jneurosci.org/content/30/26/8807.abstract
AB 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 ∼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.