Many inflammatory skin diseases are accompanied by chronic, intractable itch, but the underlying pathology is poorly understood. Here, the induction of dermatitis in mice induced chronic itch accompanied by long-term reactive astrogliosis in the dorsal horn of the spinal cord, which was dependent on STAT3 and exacerbated by gastrin-releasing peptide (GRP). Furthermore, intrathecal administration of LCN2, which is upregulated by activated astrocytes, to normal mice enhanced GRP-induced scratching — an effect that was not produced in GRP receptor-mutant mice. Thus, STAT3-activated astrocytes increase the sensation of itch via a pathway involving LCN2.