title: Activation of central trigeminovascular neurons by cortical spreading depression.
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.
  
  
  CONCLUSIONS
  We propose that CSD constitutes a nociceptive stimulus capable of activating peripheral and central trigeminovascular neurons that underlie the headache of migraine with aura.
authors.affiliation: Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Xichun
authors.initials: X
authors.lastname: Zhang
authors.forename: Dan
authors.initials: D
authors.lastname: Levy
authors.forename: Vanessa
authors.initials: V
authors.lastname: Kainz
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Noseda
authors.forename: Moshe
authors.initials: M
authors.lastname: Jakubowski
authors.forename: Rami
authors.initials: R
authors.lastname: Burstein
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001931:Brain Mapping; D013181:Cortical Spreading Depression / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000145:classification / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013268:Stimulation, Chemical; D014276:Trigeminal Nerve / Q000502:physiology*; D014279:Trigeminal Nucleus, Spinal / Q000166:cytology*