Schematic diagram of mechanisms underlying mechanical itch sensitization. Sustained activation of polymodal pruriceptive C fibers (green) sensitizes excitatory interneurons that receive convergent input from LTMRs (purple). Consequently, NK1R-expressing projection neurons (green) respond to light tactile stimuli, leading to mechanical itch sensitization. Alternatively, the disinhibition of NPY inhibitory circuits (red) may contribute to mechanical itch sensitization. +, - denote excitatory and inhibitory synapses, respectively. GRP, Gastrin Releasing Peptide; GRPR, Gastrin Releasing Peptide Receptor; LTMRs, Low-threshold mechanoreceptors; NK1R, Neurokinin 1 Receptor; NPRA, Natriuretic Peptide Receptor A; NPY, Neuropeptide Y; NPY1R, NPY1 receptor; SST, somatostatin; TLR5, Toll Like Receptor 5.