We report that: (1) Chemogenetic activation of spinal Calcrl+ neurons induces enhanced mechanical itch sensitization and increased spontaneous scratching behaviors in naïve mice; (2) Chemogenetic inhibition of spinal Calcrl+ neurons alleviates mechanical itch sensitization and spontaneous scratching behaviors in chronic itch models; (3) Chronic itch enhances intrinsic excitability of Calcrl+ neurons in chronic itch model; (4) Aβ-fiber-evoked synaptic excitation of Calcrl+ neurons is significantly amplified in chronic itch, accompanied by reduced inhibitory input. This evidence concerns the gene CALCRL and Pruritus.