**5. Puzzling Phenomenon of Pulsatile Pain: Role of Piezo?**

The headache phase of a migraine attack is characterized by pulsating (throbbing) type of headache as a specific symptom of migraine pain [30]. This puzzling migraine phenomenon has been attracting attention of many migraine researchers and already served as a basis for the famous Wollf's vascular theory of migraine headache [31]. This popular theory was supported by the clear correlation between the level of pulsations of the temporal artery and the intensity of headache during migraine attack in the patient treated with ergots [31]. Vascular mechanisms of migraine pain were also supported by the ability of the migraine mediator neuropeptide CGRP to produce the dilation of cranial vessels [32,33]. However, the role of vessels as the contributors to headache during migraine attack is still debated. As noted by Waeber and Moskowitz [34], the idea of abnormal dilatation of intracranial blood vessels leading to mechanical excitation of sensory fibers that innervate these vessels has never been validated. It is worth noting that there are also observations that the simple vasodilation of cranial vessels induced by the neuropeptide VIP is not enough to trigger migraine attack per se [35]. These findings added more intriguing aspects to the puzzling mechanisms of pulsating migraine pain. Notably, the 'vascular theory' suggested only the general explanation of pulsating migraine pain due to regular dilations of cranial vessels but it did not propose a molecular mechanism supporting this view. The discovery of Piezo mechanotransducers in trigeminal neurons suggested an attractive possibility to test these specific transducers as the sensors of the mechanical forces generated by pulsating vessels. Indeed, our recent investigation of Piezo channels in meningeal sensory nerve fibers allowed us to suggest a new model of mechanosensation in meninges during migraine attack [5].
