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

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, α-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, α-CGRP and acetylcholine (which dose-dependently increased the external carotid conductance). Another cannula was inserted intrathecally (C1-C3) for the administration of dihydroergotamine, the α2-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 μg) inhibited the vasodilatation to capsaicin, but not that to α-CGRP or acetylcholine. This inhibition was: (i) unaffected by 10 μg GR127935 or 100 μg rauwolscine, but abolished by 31 μg GR127935 or 310 μg rauwolscine at 10 μg dihydroergotamine; and (ii) abolished by the combination 10 μg GR127935100 μg rauwolscine at 100 μg dihydroergotamine. Thus, intrathecal (C1-C3) dihydroergotamine seems to inhibit the external carotid vasodilatation to capsaicin by spinal activation of serotonin 5-HT1B/1D (probably 5-HT1B) receptors and α2 (probably α2A/2C)-adrenoceptors.

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