Nevertheless, we suggested that the presence of UAs during the migraine attack might predict a good response to triptans. UAs are common in migraine patients. They have been reported in almost one out of two migraineurs (45.8%) attending a tertiary headache centre and in more than one out of four (26.9%) in a population-based study. In an open study with sumatriptan 50 mg performed on 72 migraine patients with UAs, we described pain relief in 65.3% of the patients at 1 h and in 81.9% at 2 h, while pain-free in 30.6% at 1 h and in 61.1% at 2 h. We hypothesized a large-scale recruitment of peripheral neurovascular 5-HT1B/1D receptors consequent to the activation of the trigeminal-autonomic reflex in such patients. Our hypothesis has received further confirmation by the demonstration of higher levels of calcitonin gene-related peptide, neurokinin A and vasoactive intestinal peptide (the hallmark of the activation of the trigeminal autonomic reflex) in external jugular blood in rizatriptan responders than in non-responders.