Activation of central trigeminovascular neurons by cortical spreading depression.
XiChun Zhang,Dan Levy,Vanessa Kainz,Rodrigo Noseda,Moshe Jakubowski,Rami Burstein,Rami Burstein +6 more
TLDR
It is reported that Cortical spreading depression can activate central trigeminovascular neurons in the spinal trigeminal nucleus (C1–2) of migraine headache.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 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;read more
Citations
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Pathophysiology of Migraine: A Disorder of Sensory Processing
Peter J. Goadsby,Philip R. Holland,Margarida Martins-Oliveira,Jan Hoffmann,Christoph J. Schankin,Simon Akerman +5 more
TL;DR: Investment in understanding migraine leaves us at a new dawn, able to transform its impact on a global scale, as well as understand fundamental aspects of human biology.
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Migraine pathophysiology: Anatomy of the trigeminovascular pathway and associated neurological symptoms, cortical spreading depression, sensitization, and modulation of pain
Rodrigo Noseda,Rami Burstein +1 more
TL;DR: Scientific evidence supports the notion that migraine pathophysiology involves inherited alteration of brain excitability, intracranial arterial dilatation, recurrent activation, and sensitization of the trigeminovascular pathway, and consequential structural and functional changes in genetically susceptible individuals.
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Migraine: multiple processes, complex pathophysiology.
TL;DR: Attempts to understand the headache pain itself point to activation of the trigeminovascular pathway as a prerequisite for explaining why the pain is restricted to the head, often affecting the periorbital area and the eye, and intensifies when intracranial pressure increases.
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Pathophysiology of Migraine
TL;DR: This review focuses on emerging concepts that drive the science of migraine in both a mechanistic direction and a therapeutic direction.
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Diencephalic and brainstem mechanisms in migraine
TL;DR: Dysfunction of diencephalic and brainstem nuclei that can modulate the perception of activation of the trigeminovascular system may contribute to the cascade of events that results in other symptoms of migraine — such as light and sound sensitivity — thus providing a comprehensive explanation of the neurobiology of the disorder.
References
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Journal ArticleDOI
Cellular and Molecular Mechanisms of Pain
TL;DR: Genetic, electrophysiological, and pharmacological studies are elucidating the molecular mechanisms that underlie detection, coding, and modulation of noxious stimuli that generate pain.
Journal ArticleDOI
Spreading depression of activity in the cerebral cortex
TL;DR: In this article, an interesting response elicited by electrical stimulation was noticed in the cortex of rabbits, and the distinctive feature of this response was a marked, enduring reduction of the "spontaneous" electrical activity of the cortex.
Journal ArticleDOI
Mechanisms of migraine aura revealed by functional MRI in human visual cortex
Nouchine Hadjikhani,Margarita Sanchez del Rio,Ona Wu,Denis Schwartz,Dick Bakker,Bruce Fischl,Kenneth K. Kwong,F. Michael Cutrer,Bruce R. Rosen,Roger B. H. Tootell,A. Gregory Sorensen,Michael A. Moskowitz +11 more
TL;DR: High-field functional MRI with near-continuous recording during visual aura in three subjects observed blood oxygenation level-dependent signal changes that strongly suggest that an electrophysiological event such as CSD generates the aura in human visual cortex.
Journal ArticleDOI
Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model
TL;DR: This work establishes a link between migraine aura and headache by demonstrating that cortical spreading depression activates trigeminovascular afferents and evokes a series of cortical meningeal and brainstem events consistent with the development of headache.
Journal ArticleDOI
Pathophysiology of the migraine aura. The spreading depression theory.
TL;DR: The combined experimental and clinical studies point to fruitful areas in which to look for migraine treatments of the future and provide a framework within which important aspects of the migraine attack can be modelled.
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