In summary, we demonstrate that, during chronic itch, decreased expression of Y1Rs on Tac2 neurons, a key neuron in the transmission of mechanical itch, leads to decreased inhibition of Npy neurons to Tac2 neurons, increased activity of Tac2 neurons, decreased efficacy of inhibitory synaptic transmission, and increased efficacy of excitatory synaptic transmission. Here, NPY is linked to Pruritus.