Mechanosensitive meningeal nociception via Piezo channels: Implications for pulsatile pain in migraine?

Mikhailov, Nikita; Leskinen, Jarkko; Fagerlund, Ilkka; Poguzhelskaya, Ekaterina; Giniatullina, Raisa; Gafurov, Oleg; Malm, Tarja; Karjalainen, Tero; Gröhn, Olli; Giniatullin, Rashid

doi:10.1016/j.neuropharm.2019.02.015

Cited by 63 publications

(88 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The discovery of chemical agonists of Piezo channels opened a new toolbox to investigate the function of mechanotransduction in different tissues, especially, when the traditional mechanical stimulation is not applicable or when the aim is to provide a widespread activation of Piezo channels in multiple targets. Thus, we found that the application of Yoda1 to the extended receptive field of meningeal afferents induced a massive and prolonged activation of trigeminal nerve fibers [5]. The nociceptive effect of Yoda1 in this study was reproduced by the similar prolonged activation of trigeminal mechanosensitive receptors by the hypo-osmotic solution [5].…”

Section: Unusual Chemical Activation Of Piezo Channelssupporting

confidence: 63%

“…Thus, we found that the application of Yoda1 to the extended receptive field of meningeal afferents induced a massive and prolonged activation of trigeminal nerve fibers [5]. The nociceptive effect of Yoda1 in this study was reproduced by the similar prolonged activation of trigeminal mechanosensitive receptors by the hypo-osmotic solution [5]. Moreover, Yoda1 stimulation triggered the release of CGRP (calcitonin gene-related peptide) from these trigeminal nerve fibers.…”

Section: Unusual Chemical Activation Of Piezo Channelssupporting

confidence: 57%

“…Our studies indicated that both Piezo1 and Piezo2 channels are expressed in trigeminal sensory neurons [5], which innervate head and face tissues and implicated in generation of migraine pain. Most of electrophysiological studies of Piezo channels in sensory neurons were performed by recording signaling from somas of these cells, representing a surrogate model of nerve terminals.…”

Section: Functional Properties and The Role Of Piezo1 Vs Piezo2 In Nmentioning

confidence: 70%

“…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].…”

Section: Puzzling Phenomenon Of Pulsatile Pain: Role Of Piezo?mentioning

confidence: 99%

“…However, nature of these ion channels remains unknown. Therefore, mechanosensitive Piezo channels, recently detected in human trigeminal ganglia [3,4], are the most probable candidates to mediate typical symptoms of migraine, such as mechanical hypersensitivity and pulsating type of migraine pain [5].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

The Emerging Role of Mechanosensitive Piezo Channels in Migraine Pain

Pietra

Mikhailov

Giniatullin

2020

IJMS

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Unusual Chemical Activation Of Piezo Channelssupporting

confidence: 63%

Section: Unusual Chemical Activation Of Piezo Channelssupporting

confidence: 57%

Section: Functional Properties and The Role Of Piezo1 Vs Piezo2 In Nmentioning

confidence: 70%

Section: Puzzling Phenomenon Of Pulsatile Pain: Role Of Piezo?mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Emerging Role of Mechanosensitive Piezo Channels in Migraine Pain

Pietra

Mikhailov

Giniatullin

2020

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

Multiplex epigenome editing of ion channel expression in nociceptive neurons abolished degenerative IVD‐conditioned media‐induced mechanical sensitivity

et al. 2023

View full text Add to dashboard Cite

Background Low back pain is a major contributor to disability worldwide and generates a tremendous socioeconomic impact. The degenerative intervertebral disc (IVD) has been hypothesized to contribute to discogenic pain by sensitizing nociceptive neurons innervating the disc to stimuli that is nonpainful in healthy patients. Previously, we demonstrated the ability of degenerative IVDs to sensitize neurons to mechanical stimuli; however, elucidation of degenerative IVDs discogenic pain mechanisms is required to develop therapeutic strategies that directly target these mechanisms. Aims In this study, we utilized CRISPR epigenome editing of nociceptive neurons to identify mechanisms of degenerative IVD‐induced changes to mechanical nociception and demonstrated the ability of multiplex CRISPR epigenome editing of nociceptive neurons to modulate inflammation‐induced mechanical nociception. Methods and Results Utilizing an in vitro model, we demonstrated degenerative IVD‐produced IL‐6‐induced increases in nociceptive neuron activity in response to mechanical stimuli, mediated by TRPA1, ASIC3, and Piezo2 ion channel activity. Once these ion channels were identified as mediators of degenerative IVD‐induced mechanical nociception, we developed singleplex and multiplex CRISPR epigenome editing vectors that modulate endogenous expression of TRPA1, ASIC3, and Piezo2 via targeted gene promoter histone methylation. When delivered to nociceptive neurons, the multiplex CRISPR epigenome editing vectors abolished degenerative IVD‐induced mechanical nociception while preserving nonpathologic neuron activity. Conclusion This work demonstrates the potential of multiplex CRISPR epigenome editing as a highly targeted gene‐based neuromodulation strategy for the treatment of discogenic pain, specifically; and, for the treatment of inflammatory chronic pain conditions, more broadly.

show abstract