Persistent Extracellular Signal-Regulated Kinase Activation by the Histamine H4 Receptor in Spinal Neurons Underlies Chronic Itch

The Journal of Investigative Dermatology
Kun HuangLing Zhang

Abstract

Transient extracellular signal-regulated kinase (ERK) activation in the spinal cord triggers histamine-induced acute itch. However, whether persistent ERK activation plays an important role in chronic itch development remains unclear. This study investigated the role of spinal ERK activation in chronic itch. The results showed that repetitive DNFB painting on the nape of mice evoked not only initial scratching but also sustained, spontaneous scratching. In addition, DNFB induced itching rather than nociception, as demonstrated using a cheek model. Furthermore, ERK was persistently activated in the spinal cord of DNFB-treated mice, and the intrathecal inhibition of phosphorylation of ERK suppressed both spontaneous itching and ERK activation. ERK activation was observed in neurons but not in glia cells during chronic itch development. Finally, DNFB-induced spontaneous itching behavior and ERK activation were largely inhibited by the histamine H4 receptor antagonist JNJ7777120 but not by the H1 receptor antagonist chlorpheniramine. Our results indicate that persistent ERK activation via the histamine H4 receptor in spinal neurons underlies DNFB-induced chronic itch.

Citations

Jul 31, 2018·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Gong-Hao HeWen-Ke Cai
Apr 16, 2019·Frontiers in Cellular Neuroscience·Elisa LanducciLaura Raimondi
Mar 23, 2021·Frontiers in Medicine·Xin JiaLing Zhang
Feb 8, 2020·The Journal of Investigative Dermatology·Xueting LiuAilin Tao

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