Journal Club 2015.11.26

Gate control of mechanical itch by a subpopulation of spinal cord interneurons

Light mechanical stimulation of hairy skin can induce a form of itch known as mechanical itch. This itch sensation is normally suppressed by inputs from mechanoreceptors; however, in many forms of chronic itch, including alloknesis, this gating mechanism is lost. Here we demonstrate that a population of spinal inhibitory interneurons that are defined by the expression of neuropeptide Y::Cre (NPY::Cre) act to gate mechanical itch. Mice in which dorsal NPY::Cre-derived neurons are selectively ablated or silenced develop mechanical itch without an increase in sensitivity to chemical itch or pain. This chronic itch state is histamine-independent and is transmitted independently of neurons that express the gastrin-releasing peptide receptor. Thus, our studies reveal a dedicated spinal cord inhibitory pathway that gates the transmission of mechanical itch.

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Journal Club 2015.11.19

J Allergy Clin Immunol. 2012 Sep;130(3):671-682.e4. doi: 10.1016/j.jaci.2012.05.027. Epub 2012 Jul 4.

Artemin causes hypersensitivity to warm sensation, mimicking warmth-provoked pruritus in atopic dermatitis.

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Filename : 1-s2-0-s0091674912008664-main.pdf (3 MB)
Caption :

Abstract

BACKGROUND:

Itch impairs the quality of life for many patients with dermatoses, especially atopic dermatitis (AD), and is frequently induced by a warm environment.

OBJECTIVE:

To determine the mechanism underlying itch induction by warmth, we focused on artemin, a member of glial cell line-derived neurotrophic factors (GDNFs).

METHODS:

A gene array assay revealed that artemin was expressed in substance P-treated dermal fibroblasts. The expression of artemin in healthy and AD-lesional skin was evaluated with immunohistochemistry and in situ hybridization. The impact of fibroblast-derived artemin on the proliferation and morphology of neural cell was investigated in vitro. To confirm the involvement of artemin in skin sensibility, wild-type and GDNF family receptor α3 knockout mice were employed for sensory examination.

RESULTS:

Artemin-expressing fibroblasts accumulated in skin lesions of patients with AD. Artemin induced cell proliferation of a neuroblastoma cell line in vitro, and intradermal injection of artemin in mice resulted in peripheral nerve sprouting and thermal hyperalgesia. Artemin-treated mice demonstrated scratching behavior in a warm environment, but mice deficient for GDNF family receptor α3, a potent artemin receptor, did not show this behavior. Furthermore, the escaping response to heat stimulus was attenuated in GDNF family receptor α3 knockout mice, suggesting that artemin may contribute to sensitivity to heat.

CONCLUSION:

These data suggest that dermal fibroblasts secrete artemin in response to substance P, leading to abnormal peripheral innvervation and thermal hyperalgesia. We hypothesize that artemin lowers the threshold of temperature-dependent itch sensation and might therefore be a novel therapeutic target for treating pruritic skin disorders, including AD.

Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

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