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Papers of the Week


Papers: 8 Feb 2020 - 14 Feb 2020


Animal Studies

PAIN TYPE:
Itch


2020 Feb 04


J Invest Dermatol

Spinal GRPR and NPRA contribute to chronic itch in a murine model of allergic contact dermatitis.

Authors

Liu X, Wang D, Wen Y, Zeng L, Li Y Y, Tao T, Zhao Z, Tao A
J Invest Dermatol. 2020 Feb 04.
PMID: 32032577.

Abstract

Recurrent and intractable chronic itch is a world-wide problem but mechanisms, especially the neural mechanisms, underlying chronic itch still remain unclear. In this study, we investigated the peripheral and spinal mechanisms responsible for prolonged itch in a mouse model of allergic contact dermatitis (ACD) induced by squaric acid dibutylester (SADBE). We found that repeated exposure of mice to SADBE evoked persistent spontaneous scratching and significantly aberrant cutaneous and systemic immune responses lasting for weeks. SADBE induced itch requires both nonhistaminergic and histaminergic pathways, which are likely relayed by gastrin-releasing peptide receptor (GRPR) and natriuretic peptide receptor A (NPRA) in the spinal cord respectively. Employing genetic, pharmacology, RNAscope assay and cell-specific ablation methods, we dissected a neural circuit for the prolonged itch formed as Grpr neurons act downstream of Npr1 neurons in the spinal cord. Taken together, our data suggested that targeting GRPR and NPRA may provide effective treatments for ACD associated chronic pruritus.