Central circuit mechanisms of itch

Chen, Xiaojun; Sun, Yan-Gang

doi:10.1038/s41467-020-16859-5

Cited by 101 publications

(98 citation statements)

References 126 publications

(229 reference statements)

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“…Pruriceptive information is conveyed via primary afferents from the skin and processed in the spinal dorsal horn (SDH). Recent studies have progressively advanced our understanding of the mechanism underlying neuronal circuits for itch transmission in the nervous system [ 2 – 5 ]. Specifically, gastrin-releasing peptide receptor (GRPR)-expressing (GRPR + ) neurons in the SDH act as a hub for converging pruriceptive information and are essential for producing scratching behaviors in diverse models of acute and chronic itch [ 6 – 8 ].…”

Section: Introductionmentioning

confidence: 99%

Intrinsic braking role of descending locus coeruleus noradrenergic neurons in acute and chronic itch in mice

et al. 2020

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Itch is defined as an unpleasant sensation that provokes a desire to scratch. Our understanding of neuronal circuits for itch information transmission and processing in the spinal dorsal horn (SDH) has progressively advanced following the identification of SDH neuron subsets that are crucial for scratching behavior in models of itch. However, little is known about the control of acute and chronic itch by descending signals from the brain to the SDH. In this study, using genetic approaches that enable cell-type and circuit-specific functional manipulation, we reveal an intrinsic potential of locus coeruleus (LC)-noradrenergic (NAergic) neurons that project to the SDH to control acute and chronic itch. Activation and silencing of SDH-projecting LC-NAergic neurons reduced and enhanced scratching behavior, respectively, in models of histamine-dependent and -independent acute itch. Furthermore, in a model of chronic itch associated with contact dermatitis, repetitive scratching behavior was suppressed by the activation of the descending LC-NAergic pathway and by knocking out NA transporters specific to descending LC-NAergic neurons using a CRISPR-Cas9 system. Moreover, patch-clamp recording using spinal slices showed that noradrenaline facilitated inhibitory synaptic inputs onto gastrin-releasing peptide receptor-expressing SDH neurons, a neuronal subset known to be essential for itch transmission. Our findings suggest that descending LC-NAergic signaling intrinsically controls acute and chronic itch and provide potential therapeutic strategies for the treatment of acute and chronic itch.

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Section: Introductionmentioning

confidence: 99%

Intrinsic braking role of descending locus coeruleus noradrenergic neurons in acute and chronic itch in mice

et al. 2020

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“…Once these receptors are activated, the signal is transmitted via spinal dorsal horn to the brain [ 31 ]. It was revealed, that the transmission of itch sensation by pruriceptive sensory neurons is dependent on the gastrin-releasing peptide receptor (GRPR) within the spinal cord [ 34 ], indicating a modulating effect of itch sensation within the central nervous system [ 1 ]. For example, it was demonstrated that the μ- and κ-opioid receptors interact with GRPR modifying itch perception in the spinal cord of mice [ 35 , 36 , 37 ].…”

Section: Types Of Itchmentioning

confidence: 99%

“…For example, it was demonstrated that the μ- and κ-opioid receptors interact with GRPR modifying itch perception in the spinal cord of mice [ 35 , 36 , 37 ]. More information about itch circuits and its central modulation can be found in the following reviews [ 1 , 38 , 39 ]. The succeeding paragraphs discuss peripheral receptors followed by their mediators and modulators which are reported to contribute to pruritoceptive itch sensation.…”

Section: Types Of Itchmentioning

confidence: 99%

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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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“…Ultraviolet (UV) light modifies signaling of cutenous receptors so that sensation of pruritus decreases [1]. Neurodermatitis is dermatologic condition that results from psychogenic factors.…”

Section: Introductionmentioning

confidence: 99%

The Evaluation of Narrowband Ultraviolet B Therapy in Neurodermatitis and Idiopathic Pruritus Patients

Aşkın¹,

Yücesoy²,

Uzunçakmak³

et al. 2020

jtad

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Central circuit mechanisms of itch

Cited by 101 publications

References 126 publications

Intrinsic braking role of descending locus coeruleus noradrenergic neurons in acute and chronic itch in mice

Intrinsic braking role of descending locus coeruleus noradrenergic neurons in acute and chronic itch in mice

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

The Evaluation of Narrowband Ultraviolet B Therapy in Neurodermatitis and Idiopathic Pruritus Patients

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