5-Hydroxytryptamine receptor agonists for the abortive treatment of vascular headaches block mast cell, endothelial and platelet activation within the rat dura mater after trigeminal stimulation

M. G. Buzzi, V. Dimitriadou, T. C. Theoharides, M. A. Moskowitz

Research output: Contribution to journalArticlepeer-review

Abstract

Antidromic stimulation of small caliber trigeminal axons causes neurogenic inflammation in the dura mater and tongue as evidenced by marked increases in mast cell activation, protein extravasation, as well as in the numbers of endothelial cytoplasmic vesicles, endothelial microvilli and platelet aggregates within ipsilateral post-capillary venules. In this report, we examined the effects of pretreatment with serotonin1 receptor agonists, dihydroergotamine (50 μg/kg, i.v.) and sumatriptan (100 μg/kg, i.v.) on the light and electron microscopic changes which develop after trigeminal ganglion stimulation. Both dihydroergotamine and sumatriptan are useful in the acute treatment of vascular headaches and bind with high affinity to 5-HT1(1D) receptors. Both drugs decreased significantly the number of dural vessels showing endothelial or platelet changes and the numbers of activated mast cells, but did not affect the neurogenic response in the tongue. The drugs also blocked the accumulation of horseradish peroxidase reaction product within the endothelium and perivascular space on the stimulated side. The receptor is not present on trigeminovascular fibers innervating extracranial cephalic tissues. Drug mechanism probably involves inhibition of a proximal step in the pathophysiological cascade (e.g., via activation of a prejunctional receptor) because receptors for sumatriptan have not been identified on mast cells whereas the inflammatory response was attenuated in mast cells as well as within platelets and the endothelium and (b) previous work indicates that sumatriptan and dihydroergotamine block neurotransmitter release. Hence, constriction of vascular smooth muscle mediated by postjunctional 5-hydroxytryptamine receptors is unlikely to explain the anti-inflammatory actions of dihydroergotamine or sumatriptan reported here.

Original languageEnglish
Pages (from-to)137-149
Number of pages13
JournalBrain Research
Volume583
Issue number1-2
Publication statusPublished - 1992

Keywords

  • 5-hydroxytryptamine
  • dihydroergotamine
  • mast cell
  • migraine
  • neurogenic inflammation
  • sumatriptan

ASJC Scopus subject areas

  • Neuroscience(all)

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