Intrathecal dihydroergotamine inhibits capsaicin-induced vasodilatation in the canine external carotid circulation via GR127935- and rauwolscine-sensitive receptors

BA Marichal-Cancino, A Gonzalez-Hernandez, G Manrique-Maldonado, II Ruiz-Salinas, AH Altamirano-Espinoza, Antoinette Maassen van den Brink, CM Villalon

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It has been suggested that during a migraine attack trigeminal nerves release calcitonin gene-related peptide (CGRP), producing central nociception and vasodilatation of cranial arteries, including the extracranial branches of the external carotid artery. Since trigeminal inhibition may prevent this vasodilatation, the present study has investigated the effects of intrathecal dihydroergotamine on the external carotid vasodilatation to capsaicin, alpha-CGRP and acetylcholine. Anaesthetized vagosympathectomized dogs were prepared to measure blood pressure, heart rate and external carotid conductance. A catheter was inserted into the right common carotid artery for the continuous infusion of phenylephrine (to restore the carotid vascular tone), whereas the corresponding thyroid artery was cannulated for one-min intracarotid infusions of capsaicin, alpha-CGRP and acetylcholine (which dose-dependently increased the external carotid conductance). Another cannula was inserted intrathecally (C-1-C-3) for the administration of dihydroergotamine, the alpha(2)-adrenoceptor antagonist rauwolscine or the serotonin 5-HT1B/1D receptor antagonist GR127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl) phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1-biphenyl]-4-carboxamide hydrochloride monohydrate). Intrathecal dihydroergotamine (10, 31 and 100 mu g) inhibited the vasodilatation to capsaicin, but not that to alpha-CGRP or acetylcholine. This inhibition was: (i) unaffected by 10 mu g GR127935 or 100 mu g rauwolscine, but abolished by 31 mu g GR127935 or 310 mu g rauwolscine at 10 mu g dihydroergotamine; and (ii) abolished by the combination 10 mu g GR127935 + 100 mu g rauwolscine at 100 mu g dihydroergotamine. Thus, intrathecal (C-1-C-3) dihydroergotamine seems to inhibit the external carotid vasodilatation to capsaicin by spinal activation of serotonin 5-HT1B/1D (probably 5-HT1B) receptors and alpha(2) (probably alpha(2A/2C))-adrenoceptors. (C) 2012 Elsevier B.V. All rights reserved.
Original languageUndefined/Unknown
Pages (from-to)69-77
Number of pages9
JournalEuropean Journal of Pharmacology
Issue number1-3
Publication statusPublished - 2012

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