A novel player in the field: Merkel disc in touch, itch and pain

Feng, Jing; Hu, Hongzhen

doi:10.1111/exd.13945

Cited by 16 publications

(26 citation statements)

References 48 publications

(46 reference statements)

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“…The role of Aβ-fibres in itch transmission is still disputed. In fact, recent experiments on a psoriasis mouse model suggest that a reduction in Aβ-fibres might contribute to a disinhibition of mechanical itch (20). In the current study only a minority of patients (2.7%) and controls (1.9%) reported itch after electrical stimulation at 2,000 Hz.…”

Section: Discussioncontrasting

confidence: 53%

Selective Nerve Fibre Activation in Patients with Generalized Chronic Pruritus: Hint for Central Sensitization?

Pereira¹,

Agelopoulos²,

Köllner³

et al. 2019

Acta Derm Venerol

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Mechanisms underlying chronic pruritus are not yet completely understood. We compared patients with chronic pruritus of different origins (atopic dermatitis, chronic itch on non-lesional skin, chronic prurigo) to healthy controls in regard to itch intensity and sensory symptoms elicited by electrical stimulation. Both stimulation at 5 Hz (targeting C-fibers) and 2,000 Hz (targeting Aβ-fibers) induced a higher itch intensity in patients compared to healthy individuals, regardless of the origin of the pruritus. Additionally diverse sensory symptoms were recorded between patients and controls upon electrical stimulation. These findings argue for common central sensitization mechanisms in chronic itch patients of different origins. Central sensitization induces pain augmentation in chronic pain states. An analogous mechanism is speculated for chronic pruritus. This study compared patients with chronic pruritus (n = 79) of different origins (atopic dermatitis, chronic pruritus on non-lesional skin, chronic prurigo) and healthy controls (HC, n = 54) with regard to itch intensity and qualities of sensory symptoms after selective peripheral nerve fibre activation by electrical stimulation at 5 Hz (surrogate for C-fibre function) and 2,000 Hz (surrogate for Aβ-fibre function) using a Neurometer ®. Electrically-induced itch was more intense in patients with chronic pruritus than in HC, but patients with chronic pruritus did not report "itch" more often than HC at 5 Hz. Stimulation at 2,000 Hz induced more pricking and tingling, but less throbbing in patients with chronic pruritus compared with HC. Treatment with cooling compound reduced clinical and experimental itch, but did not alter the distribution of sensory symptoms. These data show hyperknesis in chronic pruritus of various origins, arguing for common central sensitization mechanisms.

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Section: Discussioncontrasting

confidence: 53%

Selective Nerve Fibre Activation in Patients with Generalized Chronic Pruritus: Hint for Central Sensitization?

Pereira¹,

Agelopoulos²,

Köllner³

et al. 2019

Acta Derm Venerol

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“…54 Similarly, the increased epidermal expression of TRPV1 combined with a decrease of FNEs density in the elderly could question the implication of keratinocyte-sensory neuron synapticlike contacts in senile pruritus. 55,56 Keratinocytes and FNEs may act as a 2-receptor-site model, each conveying specific aspects of temperature, pain, and itch, 10,57 similar to Merkel cells 58 and the Aβ nerve fibers in the Merkel complexes. 24,59 Furthermore, both Merkel cells and keratinocytes express neural differentiation biomarkers associated with reinnervation during human cutaneous repair.…”

Section: Discussionmentioning

confidence: 99%

“…Keratinocytes and FNEs may act as a 2‐receptor‐site model, each conveying specific aspects of temperature, pain, and itch, 10,57 similar to Merkel cells 58 and the Aβ nerve fibers in the Merkel complexes 24,59 . Furthermore, both Merkel cells and keratinocytes express neural differentiation biomarkers associated with reinnervation during human cutaneous repair 60 .…”

Section: Discussionmentioning

confidence: 99%

Keratinocytes Communicate with Sensory Neurons via Synaptic‐like Contacts

Talagas

Lebonvallet

Leschiera

et al. 2020

Annals of Neurology

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Objective: Pain, temperature, and itch are conventionally thought to be exclusively transduced by the intraepidermal nerve endings. Although recent studies have shown that epidermal keratinocytes also participate in sensory transduction, the mechanism underlying keratinocyte communication with intraepidermal nerve endings remains poorly understood. We sought to demonstrate the synaptic character of the contacts between keratinocytes and sensory neurons and their involvement in sensory communication between keratinocytes and sensory neurons. Methods: Contacts were explored by morphological, molecular, and functional approaches in cocultures of epidermal keratinocytes and sensory neurons. To interrogate whether structures observed in vitro were also present in the human epidermis, in situ correlative light electron microscopy was performed on human skin biopsies. Results: Epidermal keratinocytes dialogue with sensory neurons through en passant synaptic-like contacts. These contacts have the ultrastructural features and molecular hallmarks of chemical synaptic-like contacts: narrow intercellular cleft, keratinocyte synaptic vesicles expressing synaptophysin and synaptotagmin 1, and sensory information transmitted from keratinocytes to sensory neurons through SNARE-mediated (syntaxin1) vesicle release. Interpretation: By providing selective communication between keratinocytes and sensory neurons, synaptic-like contacts are the hubs of a 2-site receptor. The permanent epidermal turnover, implying a specific en passant structure and high plasticity, may have delayed their identification, thereby contributing to the long-held concept of nerve endings passing freely between keratinocytes. The discovery of keratinocyte-sensory neuron synaptic-like contacts may call for a reassessment of basic assumptions in cutaneous sensory perception and sheds new light on the pathophysiology of pain and itch as well as the physiology of touch.

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“…Mechanosensitive pruriceptors are involved in a mechanical induced itch sensation. This touch induced itch sensation involves fading of mechanosensitive Merkel cells with advancing age (alloknesis) [ 380 , 381 ]. Recently, it was shown that the lack of Piezo2 channel signaling (modulator) in Merkel cells is responsible for the conversion of touch into itch sensation [ 382 ].…”

Section: Discussionmentioning

confidence: 99%

Advances in Understanding the Initial Steps of Pruritoceptive Itch: How the Itch Hits the Switch

Kahremany

Hofmann

Gruzman

et al. 2020

IJMS

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Pruritoceptive (dermal) itch was long considered an accompanying symptom of diseases, a side effect of drug applications, or a temporary sensation induced by invading pruritogens, as produced by the stinging nettle. Due to extensive research in recent years, it was possible to provide detailed insights into the mechanism of itch mediation and modulation. Hence, it became apparent that pruritus is a complex symptom or disease in itself, which requires particular attention to improve patients’ health. Here, we summarize recent findings in pruritoceptive itch, including how this sensation is triggered and modulated by diverse endogenous and exogenous pruritogens and their receptors. A differentiation between mediating pruritogen and modulating pruritogen seems to be of great advantage to understand and decipher the molecular mechanism of itch perception. Only a comprehensive view on itch sensation will provide a solid basis for targeting this long-neglected adverse sensation accompanying numerous diseases and many drug side effects. Finally, we identify critical aspects of itch perception that require future investigation.

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A novel player in the field: Merkel disc in touch, itch and pain

Cited by 16 publications

References 48 publications

Selective Nerve Fibre Activation in Patients with Generalized Chronic Pruritus: Hint for Central Sensitization?

Selective Nerve Fibre Activation in Patients with Generalized Chronic Pruritus: Hint for Central Sensitization?

Keratinocytes Communicate with Sensory Neurons via Synaptic‐like Contacts

Advances in Understanding the Initial Steps of Pruritoceptive Itch: How the Itch Hits the Switch

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