NDLI: Comparison of the effects of central and peripheral dopamine receptor activation on evoked firing in the trigeminocervical complex.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Charbit, Annabelle R. Akerman, Simon Goadsby, Peter J.
Description	Country affiliation: United States Author Affiliation: Charbit AR ( Department of Pharmacokinetics, Pfizer Global Research and Development, La Jolla, California 94115, USA.)
Abstract	Dopaminergic mechanisms have been suggested to play a role in migraine. Here, electrophysiological techniques were used to study the effects of intravenously administered centrally or peripherally active dopamine receptor agonists and antagonists on evoked firing in the trigeminocervical complex (TCC). After establishing baseline firing evoked by electrical stimulation of the dural middle meningeal artery (MMA) and mechanical noxious and innocuous stimulation of the ophthalmic dermatome, D(1)- or D(2)-like receptor agonists or antagonists were administered intravenously and the effect on firing was determined. In addition, with use of intravital microscopy, we monitored changes in dural vessel diameter in response to varying doses of D(1)- or D(2)-like receptor agonists to determine whether their effects were related to blood vessel caliber. The central D(2)-like receptor agonist quinpirole hydrochloride inhibited firing in the TCC evoked by stimulation of the MMA. Conversely, the central D(2)-like receptor antagonists, eticlopride hydrochloride and remoxipride hydrochloride, facilitated MMA-evoked firing and also firing evoked by noxious and innocuous stimulation of the ophthalmic dermatome. Both the peripheral D(1)-like receptor agonist fenoldopam and the central D(1)-like receptor agonists cis-(+/-)-1-(aminomethyl)-3,4-dihydro-3-phenyl-1H-2-benzopyran-5,6-diol hydrochloride (A68930 hydrochloride) and dihydrexidine facilitated innocuous brush-evoked firing, with A68930 hydrochloride having the greatest effect. The data suggest that dopamine binding to peripheral D(1)-like receptors may play a role in peripheral sensitization, and that the inhibitory or excitatory effects seen with administration of dopamine receptor agonists are independent of blood vessel changes. In addition, these studies maintain that central D(2)-like receptors inhibit trigeminocervical neurons, and may provide insight into the conflicting literature on the role of dopamine and its receptors in migraine.
File Format	HTM / HTML
ISSN	00223565
Issue Number	2
Volume Number	331
e-ISSN	15210103
Journal	Journal of Pharmacology and Experimental Therapeutics
Language	English
Publisher	American Society for Pharmacology and Experimental Therapeutics
Publisher Date	2009-11-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Research Support, Non-u.s. Gov't Electric Stimulation Injections, Intravenous Comparative Study Receptors, Dopamine Evoked Potentials Electrophysiology Male Discipline Pharmacology Peripheral Nervous System Journal Article Dopamine Agonists Pain Physiology Dopamine Antagonists Rats Rats, Sprague-dawley Pharmacology Drug Effects Physiopathology Quinpirole Receptors, Dopamine D1 Central Nervous System Animals Discipline Therapeutics Receptors, Dopamine D2 Nociceptors Trigeminal Nerve Agonists
Content Type	Text
Resource Type	Article
Subject	Molecular Medicine Pharmacology

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