Journal Club 2017.04.14

TNF-a/TNFR1 Signaling is Required for the Full Expression of Acute and Chronic Itch in Mice via Peripheral and Central Mechanisms

art10.1007s12264-017-0124-3

Xiuhua Miao1 • Ya Huang2 • Teng-Teng Liu2 • Ran Guo2 • Bing Wang2 • Xue-Long Wang3 • Li-Hua Chen4 • Yan Zhou2 • Ru-Rong Ji5,6 • Tong Liu1,2
Received: 11 November 2016 / Accepted: 9 February 2017
Ó Shanghai Institutes for Biological Sciences, CAS and Springer Science+Business Media Singapore 2017

Abstract Increasing evidence suggests that cytokines and chemokines play crucial roles in chronic itch. In the present study, we evaluated the roles of tumor necrosis factor-alpha (TNF-a) and its receptors TNF receptor subtype-1 (TNFR1) and TNFR2 in acute and chronic itch in mice. Compared to wild-type (WT) mice, TNFR1-knockout (TNFR1-KO) and TNFR1/R2 double-KO (DKO), but not TNFR2-KO mice, exhibited reduced acute itch induced by compound 48/80 and chloroquine (CQ). Application of the TNF-synthesis inhibitor thalidomide and the TNF-a antagonist etanercept dose-dependently suppressed acute itch. Intradermal injection of TNF-a was not sufficient to evoke scratching, but potentiated itch induced by com- pound 48/80, but not CQ. In addition, compound 48/80 induced TNF-a mRNA expression in the skin, while CQ induced its expression in the dorsal root ganglia (DRG) and spinal cord. Furthermore, chronic itch induced by dry skin was reduced by administration of thalidomide and etaner- cept and in TNFR1/R2 DKO mice. Dry skin induced TNF- a expression in the skin, DRG, and spinal cord and TNFR1 expression only in the spinal cord. Thus, our findings suggest that TNF-a/TNFR1 signaling is required for the full expression of acute and chronic itch via peripheral and central mechanisms, and targeting TNFR1 may be benefi- cial for chronic itch treatment.
Keywords Itch Tumor necrosis factor Tumor necrosis factor receptor Spinal cord Central sensitization