Chronic itchiness is a symptom of many different skin diseases. The development of the itch sensation is triggered by sensory neurons and this signal is then transferred to the brain. G-coupled protein receptor (GPCR) pathways are thought to convey the itch signal and dysregulation of these pathways promotes chronic itch development. Zhong-Qiu Zhao and colleagues at Washington University developed a mouse model of chronic itch, in which a constitutively active form of the serine-threonine kinase BRAF was expressed in sensory neurons (BRAFNav1.8 mice). Compared to wild-type mice, these mice exhibited more spontaneous itch behavior and developed an enhanced scratching response to pruritogens. The authors found that BRAFNav1.8 mice had enhanced expression of the gene encoding the itch-sensing gastrin-releasing peptide receptor (GRPR), which sustained activation of ERK in neurons and the itch sensation. Pharmacological inhibition of BRAF and subsequent GRPR signaling attenuated itch sensation in the chronic itch mouse model. The above image illustrates the increase of pERK+ cells as indicated by double staining with pERK (red) and IB4 (green) in dorsal root ganglia from a BRAFNav1.8 mouse.
Chronic itch, or pruritus, is associated with a wide range of skin abnormalities. The mechanisms responsible for chronic itch induction and persistence remain unclear. We developed a mouse model in which a constitutively active form of the serine/threonine kinase BRAF was expressed in neurons gated by the sodium channel Nav1.8 (BRAFNav1.8 mice). We found that constitutive BRAF pathway activation in BRAFNav1.8 mice results in ectopic and enhanced expression of a cohort of itch-sensing genes, including gastrin-releasing peptide (
Zhong-Qiu Zhao, Fu-Quan Huo, Joseph Jeffry, Lori Hampton, Shadmehr Demehri, Seungil Kim, Xian-Yu Liu, Devin M. Barry, Li Wan, Zhong-Chun Liu, Hui Li, Ahu Turkoz, Kaijie Ma, Lynn A. Cornelius, Raphael Kopan, James F. Battey Jr., Jian Zhong, Zhou-Feng Chen