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  • Letter to the Editor
  • Open Access

Reply to Elliot Shevel

  • 1Email author,
  • 1,
  • 1 and
  • 1
The Journal of Headache and Pain201213:435

Received: 21 February 2012

Accepted: 28 February 2012

Published: 20 March 2012


  • Migraine
  • Calcitonin
  • Middle Cerebral Artery
  • Migraine Attack
  • External Carotid

In a recent review article we reconsidered the hypothesis that neurogenic vasodilatation is a key factor in the genesis of the headache of the migraine attack according to an updated and critical analysis of past and current literature. Cited papers span from pioneering studies in experimental animals of more than a century ago, to very recent investigations in humans in whom vasodilatation of cranial arteries has been accurately measured with highly sophisticated and reliable techniques. Results of neurovascular imaging studies have strongly corroborated previous pharmacological acquisition with antagonists of the calcitonin gene-related peptide receptor. Findings from clinical trials with these drugs underlined the role of neurogenic vasodilatation in migraine. In a comment to our review [1], Elliot Shevel [2] has appropriately noted that Zwetsloot et al. [3] and Schoonman et al. [4] indeed studied the middle cerebral artery and intracranial vessels and the last 10 mm of the external carotid artery. Dr. Shevel also noted that the papers by Ashina et al. [5] and Wienecke et al. [6] were performed in healthy volunteers in whom headache and not migraine-like pain was studied. Thus, all these findings do not negate the proposal by Graham and Woolf (sustained in our review article) that pertains to migraineurs and to the temporal artery (possibly limited to other extracranial arteries). Therefore, we thank Dr. Shevel for his observations that further support the view that vasodilatation brought about by activation of perivascular peptidergic nerve fibers should be considered as a major mechanism in migraine. This was, in fact, the main purpose of our review article.

On the other hand, we acknowledge that the complex pathophysiology of migraine and the mystery that still covers the initiating factors/mechanisms of the migraine attack should cast caution in refusing the contribution of triggers located in the central nervous system.


Conflict of interest


Open Access

This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

Authors’ Affiliations

Headache Centre, Careggi University Hospital, University of Florence, Florence, Italy


  1. Geppetti P, Rossi E, Chiarugi A, Benemei S (2012) Antidromic vasodilatation and the migraine mechanism. J Headache Pain 13:103–111, 22200764, 10.1007/s10194-011-0408-3PubMed CentralView ArticlePubMedGoogle Scholar
  2. Shevel E (2012) Comments on the review article ‘Antidromic vasodilatation and the migraine mechanism’ by Gepetti et al. in the Journal of Headache and Pain 2012. 13:103–111. J Headache Pain. doi:10.1007/s10194-012-0431-z
  3. Zwetsloot CP, Caekebeke JF, Ferrari MD (1993) Lack of asymmetry of middle cerebral artery blood velocity in unilateral migraine. Stroke 24:1335–1338, 8362427, 10.1161/01.STR.24.9.1335, 1:STN:280:DyaK3szmvFymsw%3D%3DView ArticlePubMedGoogle Scholar
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  6. Wienecke T, Olesen J, Ashina M (2011) Discrepancy between 827 strong cephalic arterial dilatation and mild headache caused by prostaglandin D (PGD). Cephalalgia 31:65–76, 20974593, 10.1177/0333102410373156View ArticlePubMedGoogle Scholar


© The Author(s) 2012


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