Activation of central trigeminovascular neurons by cortical spreading depression

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


Objective: 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).

Methods: 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.

Results: 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.

Interpretation: We propose that CSD constitutes a nociceptive stimulus capable of activating peripheral and central trigeminovascular neurons that underlie the headache of migraine with aura.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Brain Mapping
  • Cortical Spreading Depression / physiology*
  • Male
  • Neurons / classification
  • Neurons / physiology*
  • Nociceptors / physiology
  • Physical Stimulation / methods
  • Rats
  • Rats, Sprague-Dawley
  • Statistics, Nonparametric
  • Stimulation, Chemical
  • Trigeminal Nerve / physiology*
  • Trigeminal Nucleus, Spinal / cytology*