*Review* **The Emerging Role of Mechanosensitive Piezo Channels in Migraine Pain**

**Adriana Della Pietra 1, Nikita Mikhailov <sup>1</sup> and Rashid Giniatullin 1,2,\***


Received: 12 December 2019; Accepted: 19 January 2020; Published: 21 January 2020

**Abstract:** Recently discovered mechanosensitive Piezo channels emerged as the main molecular detectors of mechanical forces. The functions of Piezo channels range from detection of touch and pain, to control of the plastic changes in different organs. Recent studies suggested the role of Piezo channels in migraine pain, which is supposed to originate from the trigeminovascular nociceptive system in meninges. Interestingly, migraine pain is associated with such phenomenon as mechanical hypersensitivity, suggesting enhanced mechanotransduction. In the current review, we present the data that propose the implication of Piezo channels in migraine pain, which has a distinctive pulsatile character. These data include: (i) distribution of Piezo channels in the key elements of the trigeminovascular nociceptive system; (ii) the prolonged functional activity of Piezo channels in meningeal afferents providing a mechanistical basis for mechanotransduction in nociceptive nerve terminals; (iii) potential activation of Piezo channels by shear stress and pulsating blood flow; and (iv) modulation of these channels by emerging chemical agonists and modulators, including pro-nociceptive compounds. Achievements in this quickly expanding field should open a new road for efficient control of Piezo-related diseases including migraine and chronic pain.

**Keywords:** Piezo channels; mechanotransduction; pain; migraine; CGRP
