Itch can be suppressed by painful stimuli, but the underlying neural basis is unknown.We generated conditional null mice in which VGLUT2-dependent synaptic glutamate release from mainly Nav 1.8-expressing nociceptors was abolished.These mice showed deficits in pain behaviors including mechanical pain, heat pain, capsaicin-evoked pain, inflammatory pain and neuropathic pain.The pain deficits were accompanied by greatly enhanced itching, as suggested by i) sensitization of both histamine-dependent and histamine-independent itch pathways, and ii) development of spontaneous scratching and skin lesions.Strikingly, intradermal capsaicin injection promotes itch responses, as opposed to pain responses in control littermates.The conditional Vglut2 mutant mice thereby emulate human chronic itch syndromes in which painful stimuli paradoxically promote itch.Our studies suggest that synaptic glutamate release from a group of peripheral nociceptors is required to sense pain and suppress itch.Elimination of VGLUT2 in these nociceptors creates a mouse model of chronic neurogenic itch.