There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Itch is described as an irritating sensation that triggers a desire to scratch. However, this definition hardly seems fitting for the millions of people who suffer from intractable itch. Indeed, the Buddhist philosopher Nāgārjuna more aptly stated, "There is pleasure when an itch is scratched. But to be without an itch is more pleasurable still." Chronic itch is widespread and very difficult to treat. In this review we focus on the molecules, cells and circuits in the peripheral and central nervous systems that drive acute and chronic itch transmission. Understanding the itch circuitry is critical to developing new therapies for this intractable disease.

Related collections

Most cited references 82

Record: found
Abstract: found
Article: not found

The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch.

Sarah R. Wilson, Lydia Thé, Lyn M. Batia … (2013)

Atopic dermatitis (AD) is a chronic itch and inflammatory disorder of the skin that affects one in ten people. Patients suffering from severe AD eventually progress to develop asthma and allergic rhinitis, in a process known as the "atopic march." Signaling between epithelial cells and innate immune cells via the cytokine thymic stromal lymphopoietin (TSLP) is thought to drive AD and the atopic march. Here, we report that epithelial cells directly communicate to cutaneous sensory neurons via TSLP to promote itch. We identify the ORAI1/NFAT calcium signaling pathway as an essential regulator of TSLP release from keratinocytes, the primary epithelial cells of the skin. TSLP then acts directly on a subset of TRPA1-positive sensory neurons to trigger robust itch behaviors. Our results support a model whereby calcium-dependent TSLP release by keratinocytes activates both primary afferent neurons and immune cells to promote inflammatory responses in the skin and airways. Copyright © 2013 Elsevier Inc. All rights reserved.

0 comments Cited 307 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria.

Marcus Maurer, Karin Rosén, Hsin-Ju Hsieh … (2013)

Many patients with chronic idiopathic urticaria (also called chronic spontaneous urticaria) do not have a response to therapy with H-antihistamines, even at high doses. In phase 2 trials, omalizumab, an anti-IgE monoclonal antibody [corrected] that targets IgE and affects mast-cell and basophil function, has shown efficacy in such patients. In this phase 3, multicenter, randomized, double-blind study, we evaluated the efficacy and safety of omalizumab in patients with moderate-to-severe chronic idiopathic urticaria who remained symptomatic despite H-antihistamine therapy (licensed doses). We randomly assigned 323 patients to receive three subcutaneous injections, spaced 4 weeks apart, of omalizumab at doses of 75 mg, 150 mg, or 300 mg or placebo, followed by a 16-week observation period. The primary efficacy outcome was the change from baseline in a weekly itch-severity score (ranging from 0 to 21, with higher scores indicating more severe itching). The baseline weekly itch-severity score was approximately 14 in all four study groups. At week 12, the mean (±SD) change from baseline in the weekly itch-severity score was -5.1±5.6 in the placebo group, -5.9±6.5 in the 75-mg group (P=0.46), -8.1±6.4 in the 150-mg group (P=0.001), and -9.8±6.0 in the 300-mg group (P<0.001). Most prespecified secondary outcomes at week 12 showed similar dose-dependent effects. The frequency of adverse events was similar across groups. The frequency of serious adverse events was low, although the rate was higher in the 300-mg group (6%) than in the placebo group (3%) or in either the 75-mg or 150-mg group (1% for each). Omalizumab diminished clinical symptoms and signs of chronic idiopathic urticaria in patients who had remained symptomatic despite the use of approved doses of H-antihistamines. (Funded by Genentech and Novartis Pharma; ClinicalTrials.gov number, NCT01292473.).

0 comments Cited 278 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

A subpopulation of nociceptors specifically linked to itch

Liang Han, Chao Ma, Qin Liu … (2012)

Itch-specific neurons have been sought for decades. The existence of such neurons is in doubt recently due to the observation that itch-mediating neurons also respond to painful stimuli. Here, we genetically labeled and manipulated MrgprA3+ neurons in dorsal root ganglion (DRG) and found that they exclusively innervate the epidermis of the skin and respond to multiple pruritogens. Ablation of MrgprA3+ neurons led to significant reductions in scratching evoked by multiple pruritogens and occurring spontaneously under chronic itch conditions whereas pain sensitivity remained intact. Importantly, mice with TRPV1 exclusively expressed in MrgprA3+ neurons exhibited only itch- and not pain behavior in response to capsaicin. Although MrgprA3+ neurons are sensitive to noxious heat, activation of TRPV1 in these neurons by noxious heat did not alter pain behavior. These data suggest that MrgprA3 defines a specific subpopulation of DRG neurons mediating itch. Our study opens new avenues for studying itch and developing anti-pruritic therapies.

0 comments Cited 204 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

PubMed ID:: 24473265

PMC ID:: 4364402

DOI:: 10.1038/nn.3619

ScienceOpen disciplines: Chemistry

Keywords: Animals,Central Nervous System,pathology,Humans,Models, Biological,Peripheral Nerves,physiopathology,Pruritus,Sensation,Signal Transduction

Data availability:

ScienceOpen disciplines: Chemistry

Keywords: Animals, Central Nervous System, pathology, Humans, Models, Biological, Peripheral Nerves, physiopathology, Pruritus, Sensation, Signal Transduction

Comments

Comment on this article

scite_

Smart Citations

Citing PublicationsSupportingMentioningContrasting

View Citations

See how this article has been cited at scite.ai

scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.

Why we scratch an itch: the molecules, cells and circuits of itch.

Read this article at

Abstract

Related collections

Gamma Delta T cells

Most cited references 82

The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch.

Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria.

A subpopulation of nociceptors specifically linked to itch

Author and article information

Journal

Comments

Comment on this article

Similar content 210

Cited by 115

Most referenced authors 933