Differential effects of the Piezo1 agonist Yoda1 in the trigeminovascular system: An electrophysiological and intravital microscopy study in rats

• Published in: Experimental neurology 2021-05, Vol.339, p.113634-113634, Article 113634
• Main Authors: Dolgorukova, Antonina, Isaeva, Julia E., Verbitskaya, Elena, Lyubashina, Olga A., Giniatullin, Rashid А., Sokolov, Alexey Y.
• Format: Article
• Language: English
• Subjects: Dura mater; Mechanosensitivity; Migraine; Piezo1 channels; Trigeminovascular system; Yoda1
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2021.113634

Migraine is associated with the activation and sensitisation of the trigeminovascular system and is often accompanied by mechanical hyperalgesia and allodynia. The mechanisms of mechanotransduction during a migraine attack are yet unknown. We have proposed that the ion channel Piezo1 may be involved, since it is expressed in endothelial cells as well as in trigeminal ganglion neurons, and thus, may contribute to the activation of both the vascular and neuronal component of the trigeminovascular system. We took advantage of extracellular recordings from the trigeminocervical complex – a key relay centre in the migraine pain pathway, to directly assess the impact of the differently applied Piezo1 agonist Yoda1 on the sensory processing at the spinal level. At a low dose, Yoda1 slightly facilitated the ongoing firing of central trigeminovascular neurons, however, at a high dose, this substance contributed to the suppression of their activity. Using intravital microscopy, we have revealed that Yoda1 at high dose can also induce the dilation of meningeal arteries innervated by trigeminal afferents. Collectively, here we have identified both neuronal and vascular modulation via selective activation of mechanosensitive Piezo1 channels, which provide new evidence in favour of the Piezo1 role in migraine pathogenesis. We propose several mechanisms that may underlie the revealed effects of Yoda1. [Display omitted] •We show the opposite effect of low and high Yoda1 doses after its dural application•At 25 μM, Yoda1 facilitated ongoing firing of 2nd-order trigeminovascular neurons•At 500 μM, this drug induced suppression of the trigeminal neurons' ongoing activity•Meningeal arteries dilated after the high Yoda1 dose of 500 μM•Piezo1 is involved in migraine-related mechanisms in the trigeminovascular system