• Pierangelo Geppetti, Eleonora Rossi, Alberto Chiarugi, and Silvia Benemei.
• Headache Centre, Careggi University Hospital, Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy. geppetti@unifi.it
• J Headache Pain. 2012 Mar 1; 13 (2): 103-11.

AbstractDespite the fact that an unprecedented series of new discoveries in neurochemistry, neuroimaging, genetics and clinical pharmacology accumulated over the last 20 years has significantly increased our current knowledge, the underlying mechanism of the migraine headache remains elusive. The present review article addresses, from early evidence that emerged at the end of the nineteenth century, the role of 'antidromic vasodilatation' as part of the more general phenomenon, currently defined as neurogenic inflammation, in the unique type of pain reported by patients suffering from migraine headaches. The present paper describes distinctive orthodromic and antidromic properties of a subset of somatosensory neurons, the vascular- and neurobiology of peptides contained in these neurons, and the clinical-pharmacological data obtained in recent investigations using provocation tests in experimental animals and human beings. Altogether, previous and recent data underscore that antidromic vasodilatation, originating from the activation of peptidergic somatosensory neurons, cannot yet be discarded as a major contributing mechanism of the throbbing head pain and hyperalgesia of migraine.© The Author(s) 2011. This article is published with open access at Springerlink.com

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