Dopamine inhibits trigeminovascular transmission in the rat.
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.


CONCLUSIONS
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.
Bergerot
Astrid
A
Headache Group, Institute of Neurology, and National Hospital for Neurology and Neurosurgery, London, United Kingdom.
Storer
Robin J
RJ
Goadsby
Peter J
PJ
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D001931:Brain Mapping; D004298:Dopamine / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D008297:Male; D008578:Meninges / Q000098:blood supply*; D008839:Microelectrodes; D009474:Neurons; D009619:Nociceptors / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine; D009435:Synaptic Transmission / Q000502:physiology*; D014278:Trigeminal Nuclei / Q000378:metabolism*
D011954:Receptors, Dopamine; D004298:Dopamine