Send to

Choose Destination
Ann Neurol. 2011 May;69(5):855-65. doi: 10.1002/ana.22329. Epub 2011 Mar 17.

Activation of central trigeminovascular neurons by cortical spreading depression.

Author information

Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center, Boston, MA, USA.



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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center