A subpopulation of nociceptors specifically linked to itch

Itch-specific neurons have been sought for decades. The existence of such neurons is in doubt recently due to the observation that itch-mediating neurons also respond to painful stimuli. Here, we genetically labeled and manipulated MrgprA3(+) neurons in dorsal root ganglion (DRG) and found that they exclusively innervate the epidermis of the skin and respond to multiple pruritogens. Ablation of MrgprA3(+) neurons led to significant reductions in scratching evoked by multiple pruritogens and occurring spontaneously under chronic itch conditions whereas pain sensitivity remained intact. Importantly, mice with TRPV1 exclusively expressed in MrgprA3(+) neurons exhibited only itch- and not pain behavior in response to capsaicin. Although MrgprA3(+) neurons are sensitive to noxious heat, activation of TRPV1 in these neurons by noxious heat did not alter pain behavior. These data suggest that MrgprA3 defines a specific subpopulation of DRG neurons mediating itch. Our study opens new avenues for studying itch and developing anti-pruritic therapies.