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Abstract

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. ANN NEUROL 2011;