Spinal dorsal horn astrogliosis facilitates itch transmission in a mouse model of contact dermatitis.

Abstract

Chronic itch is a major symptom in various skin diseases, such as atopic and contact dermatitis, but its mechanism remains to be determined. We have previously shown that spinal dorsal horn (SDH) astrocytes become activated in mouse models of chronic itch and that astrocyte-derived lipocalin-2 (LCN2) is crucial for maintaining chronic itching. However, how LCN2 enhances spinal itch neurotransmission is not understood. In this study, using Gastrin-releasing peptide receptor (Grpr)-egfp mice to label itch-specific neurons in SDH, we found GRP-induced depolarization of excitatory GRPR⁺ neurons was greatly potentiated in contact dermatitis model mice. Genetic inhibition of signal transducer and activator transcription 3 (STAT3) in SDH astrocytes ameliorated chronic itch and also normalized enhancement of GRP-induced depolarization of excitatory GRPR⁺ neurons in chronic itch model. Furthermore, coadministration of LCN2 and GRP also potentiated GRP-induced depolarization of excitatory GRPR⁺ neurons. Our finding indicate that reactive astrocytes facilitated SDH itch transmission in chronic itch via upregulated LCN2.