Sensory Schwann cells set perceptual thresholds for touch and selectively regulate mechanical nociception

Ojeda-Alonso, Julia; Calvo-Enrique, Laura; Paricio-Montesinos, Ricardo; Kumar, Rakesh; Zhang, Ming-Dong; Poulet, James F. A.; Ernfors, Patrik; Lewin, Gary R.

doi:10.1038/s41467-024-44845-8

Cited by 7 publications

(1 citation statement)

References 54 publications

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“…Nevertheless, Shin et al [ 14 , 15 ] observed the presence of PIEZO1 and PIEZO2 in both the axon and non-neuronal cells of rat CEOCs, while Yamanishi and Iwabuchi [ 20 , 21 ] revealed PIEZO2 expression in both the axon and terminal glial cells of human lanceolate nerve endings. This double cellular localization of mechano-gated protein in the axons and associated terminal glial cells of sensory corpuscles is of great interest because evidence is being accumulated that not only axons but also non-neuronal cells participate in touch detection [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Axonal and Glial PIEZO1 and PIEZO2 Immunoreactivity in Human Clitoral Krause’s Corpuscles

Cuendias,

Vega,

García-Suárez

et al. 2024

IJMS

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Krause’s corpuscles are typical of cutaneous mucous epithelia, like the lip vermillion or the glans clitoridis, and are associated with rapidly adapting low-threshold mechanoreceptors involved in gentle touch or vibration. PIEZO1 and PIEZO2 are transmembrane mechano-gated proteins that form a part of the cationic ion channels required for mechanosensitivity in mammalian cells. They are involved in somatosensitivity, especially in the different qualities of touch, but also in pain and proprioception. In the present study, immunohistochemistry and immunofluorescence were used to analyze the occurrence and cellular location of PIEZO1 and PIEZO2 in human clitoral Krause’s corpuscles. Both PIEZO1 and PIEZO2 were detected in Krause’s corpuscles in both the axon and the terminal glial cells. The presence of PIEZOs in the terminal glial cells of Kraus’s corpuscles is reported here for the first time. Based on the distribution of PIEZO1 and PIEZO2, it may be assumed they could be involved in mechanical stimuli, sexual behavior, and sexual pleasure.

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Section: Introductionmentioning

confidence: 99%

Axonal and Glial PIEZO1 and PIEZO2 Immunoreactivity in Human Clitoral Krause’s Corpuscles

Cuendias,

Vega,

García-Suárez

et al. 2024

IJMS

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Origin, identity, and function of terminal Schwann cells

Hastings,

Valdez

2024

Trends in Neurosciences

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Piezo2 voltage-block regulates mechanical pain sensitivity

Sánchez-Carranza,

Chakrabarti,

Kühnemund

et al. 2024

Brain

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PIEZO2 is a trimeric mechanically-gated ion channel expressed by most sensory neurones in the dorsal root ganglia. Mechanosensitive PIEZO2 channels are also genetically required for normal touch sensation in both mice and humans. We previously showed that PIEZO2 channels are also strongly modulated by membrane voltage. Specifically, it is only at very positive voltages that all channels are available for opening by mechanical force. Conversely, most PIEZO2 channels are blocked at normal negative resting membrane potentials. The physiological function of this unusual biophysical property of PIEZO2 channels, however, remained unknown. We characterized the biophysical properties of three PIEZO2 ion channel mutations at an evolutionarily conserved Arginine (R2756). Using genome engineering in mice we generated Piezo2R2756H/R2756H and Piezo2R2756K/R2756K knock-in mice to characterize the physiological consequences of altering PIEZO2 voltage sensitivity in vivo. We measured endogenous mechanosensitive currents in sensory neurones isolated from the dorsal root ganglia and characterized mechanoreceptor and nociceptor function using electrophysiology. Mice were also assessed behaviourally and morphologically. Mutations at the conserved Arginine (R2756) dramatically changed the biophysical properties of the channel relieving voltage block and lowering mechanical thresholds for channel activation. Piezo2R2756H/R2756H and Piezo2R2756K/R2756K knock-in mice that were homozygous for gain of function mutations were viable and were tested for sensory changes. Surprisingly, mechanosensitive currents in nociceptors, neurones that detect noxious mechanical stimuli, were substantially sensitized in Piezo2 knock-in mice, but mechanosensitive currents in most mechanoreceptors that underlie touch sensation were only mildly affected by the same mutations. Single-unit electrophysiological recordings from sensory neurones innervating the glabrous skin revealed that rapidly-adapting mechanoreceptors that innervate Meissner’s corpuscles exhibited slightly decreased mechanical thresholds in Piezo2 knock-in mice. Consistent with measurements of mechanically activated currents in isolated sensory neurones essentially all cutaneous nociceptors, both fast conducting Aδ-mechanonociceptors and unmyelinated C-fibre nociceptors were substantially more sensitive to mechanical stimuli and indeed acquired receptor properties similar to ultrasensitive touch receptors in Piezo2 knock-in mice. Mechanical stimuli also induced enhanced ongoing activity in cutaneous nociceptors in Piezo2 knock-in mice and hyper-sensitive PIEZO2 channels were sufficient alone to drive ongoing activity, even in isolated nociceptive neurones. Consistently, Piezo2 knock-in mice showed substantial behaviourally hypersensitivity to noxious mechanical stimuli. Our data indicate that ongoing activity and sensitization of nociceptors, phenomena commonly found in human chronic pain syndromes, can be driven by relieving the voltage-block of PIEZO2 ion channels. Indeed, membrane depolarization caused by multiple noxious stimuli may sensitize nociceptors by relieving voltage-block of PIEZO2 channels.

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Sensory Schwann cells set perceptual thresholds for touch and selectively regulate mechanical nociception

Cited by 7 publications

References 54 publications

Axonal and Glial PIEZO1 and PIEZO2 Immunoreactivity in Human Clitoral Krause’s Corpuscles

Axonal and Glial PIEZO1 and PIEZO2 Immunoreactivity in Human Clitoral Krause’s Corpuscles

Origin, identity, and function of terminal Schwann cells

Piezo2 voltage-block regulates mechanical pain sensitivity

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