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Papers of the Week


Papers: 10 Oct 2020 - 16 Oct 2020


Animal Studies

PAIN TYPE:
Itch


2020 Oct 08


J Invest Dermatol

GRPR/ERK and NPRA/ERK Signaling Pathways Play a Critical Role in Spinal Transmission of Chronic Itch.

Authors

Liu X, Wang Y, Tao T, Zeng L, Wang D, Wen Y, Li Y Y, Zhao Z, Tao A
J Invest Dermatol. 2020 Oct 08.
PMID: 33039402.

Abstract

Intractable or recurrent chronic itch greatly reduces the patients' quality of life and impairs their daily activities. In this study, we investigated whether there are certain key signaling molecules downstream of the recently identified peptides mediating itch in the spinal cord. RNA sequencing analysis of mouse spinal cord in chronic itch models induced by squaric acid dibutylester and imiquimod showed that extracellular signal-regulated kinase 1/2 (ERK1/2) cascade is the most significantly up-regulated gene cluster in both models. In four different mouse models of chronic itch, sustained ERK phosphorylation was detected mainly in spinal neurons, and MEK inhibitors significantly inhibited chronic itch in these models. Phosphorylated ERK (pERK) was observed in interneurons expressing receptors of different neuropeptides for itch, including GRPR, NPRA, NMBR or sst. Blocking GRPR and NPRA by genetic approaches or toxins in mice significantly attenuated or ablated spinal pERK. When HEK293T cells transfected with these receptors were exposed to their respective agonists, ERK was the most significantly activated intracellular signaling molecule. Together, our work showed that pERK is a unique marker for itch signal transmission in the spinal cord and an attractive target for the treatment of chronic itch.