Activation of central trigeminovascular neurons by cortical spreading depression
Article first published online: 17 MAR 2011
Copyright © 2011 American Neurological Association
Annals of Neurology
Volume 69, Issue 5, pages 855–865, May 2011
How to Cite
Zhang, X., Levy, D., Kainz, V., Noseda, R., Jakubowski, M. and Burstein, R. (2011), Activation of central trigeminovascular neurons by cortical spreading depression. Ann Neurol., 69: 855–865. doi: 10.1002/ana.22329
- Issue published online: 22 APR 2011
- Article first published online: 17 MAR 2011
- Accepted manuscript online: 17 NOV 2010 11:06AM EST
- Manuscript Accepted: 8 NOV 2010
- Manuscript Revised: 13 OCT 2010
- Manuscript Received: 13 AUG 2010
Cortical spreading depression (CSD) has long been implicated in migraine attacks that begin with visual aura. Having shown that a wave of CSD can trigger long-lasting activation of meningeal nociceptors—the first-order neurons of the trigeminovascular pathway thought to underlie migraine headache—we now report that CSD can activate central trigeminovascular neurons in the spinal trigeminal nucleus (C1–2).
Stimulation of the cortex with pinprick or KCl granule was used to induce CSD in anesthetized rats. Neuronal activity was monitored in C1–2 using single-unit recording.
In 25 trigeminovascular neurons activated by CSD, mean firing rate (spikes/s) increased from 3.6 ± 1.2 before CSD (baseline) to 6.1 ± 1.8 after CSD (p < 0.0001) for a period >13 minutes. Neuronal activity returned to baseline level after 30.0 ± 3.1 minutes in 14 units, and remained elevated for 66.0 ± 8.3 (22–108) minutes through the entire recording period in the other 11 units. Neuronal activation began within 0.9 ± 0.4 (0–2.5) minutes after CSD in 7 neurons located in laminae I–II, or after a latency of 25.1 ± 4.0 (7–75) minutes in 9 neurons located in laminae I–II, and 9 neurons located in laminae III–V. In 27 trigeminovascular neurons not activated by CSD, mean firing rate was 2.0 ± 0.7 at baseline and 1.8 ± 0.7 after CSD.
We propose that CSD constitutes a nociceptive stimulus capable of activating peripheral and central trigeminovascular neurons that underlie the headache of migraine with aura. ANN NEUROL 2011;