Dopamine inhibits trigeminovascular transmission in the rat

Authors

  • Astrid Bergerot PhD,

    1. Headache Group, Institute of Neurology, and National Hospital for Neurology and Neurosurgery, London, United Kingdom
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  • Robin J. Storer PhD,

    1. Headache Group, Institute of Neurology, and National Hospital for Neurology and Neurosurgery, London, United Kingdom
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  • Peter J. Goadsby MD, PhD, DSc, FRACP, FRCP

    Corresponding author
    1. Headache Group, Institute of Neurology, and National Hospital for Neurology and Neurosurgery, London, United Kingdom
    • Institute of Neurology, Queen Square, London, WC1N 3BG, United Kingdom
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Abstract

Objective

Clinical evidence, such as premonitory or postdromal symptoms, indicate involvement of dopamine in the pathophysiology of migraine.

Methods

To study the influence of dopamine on nociceptive trigeminovascular neurotransmission, we first determined using immunohistofluorescence that dopamine receptors were present in the rat trigeminocervical complex; then using extracellular recording techniques, we examined whether dopamine modulates cell firing in the trigeminocervical complex.

Results

We identified a discrete population of D1 receptors (median, 11; interquartile range, 7–30 neurons/hemisection) predominantly located in the deep laminae and a more abundant population of D2 receptors (median,75; interquartile range, 30–99 neurons/hemisection) that were evenly distributed in the trigeminocervical complex. Intravenous dopamine had no effect on trigeminovascular neurons, whereas when dopamine was applied microiontophoretically, a potent reversible inhibition of L-glutamate–evoked firing was observed. The effect of microiontophoretically applied dopamine was dose dependent. Dopamine also strongly inhibited activation of trigeminocervical neurons in response to middle meningeal artery stimulation in vivo with a maximum effect obtained within 10 minutes after the application and return to baseline within 30 minutes.

Interpretation

We conclude that central dopamine-containing neurons may play a role in modulating trigeminovascular nociception; these neurons offer an important target that will expand our understanding of migraine and may offer new directions for therapy. Ann Neurol 2007;61:251–262

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