Chronic itch is a cardinal symptom observed in patients with atopic and contact dermatitis for which existing treatments are largely ineffective.  A subset of excitatory neurons in the spinal dorsal horn (SDH) that expresses gastrin-releasing peptide receptors (GRPR) is critical for itch transmission.  Despite recent progress in our understanding of itch transmission circuitry, the mechanism underlying chronic itch remains largely unknown.  We have recently shown that GRP-induced excitability of GRPR⁺ SDH neurons is potentiated in a mouse model of chronic itch and that this sensitization requires a non-cell-autonomous signal from SDH astrocytes—glial cells that are activated under chronic itch conditions. In fact, suppressing the reactive astrocytes or decreasing LCN2 expression attenuates the potentiation of GRP-induced neuronal excitation.  Furthermore, glutamatergic excitatory inputs onto GRPR⁺ SDH neurons are also strengthened under chronic itch conditions.  This involves a DRG neuron-derived factor whose expression is upregulated by dermatitis. In my talk, I will show a model of the mechanism underlying the sensitization of GRPR⁺ itch transmission neurons in the SDH by signals from glia and primary afferents.