RT Journal Article
SR Electronic
T1 Presynaptic inhibition of cutaneous afferents prevents chronic itch
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 806976
DO 10.1101/806976
A1 Augusto Escalante
A1 Rüdiger Klein
YR 2019
UL http://biorxiv.org/content/early/2019/10/16/806976.abstract
AB Chronic itch represents an incapacitating burden on patients suffering a wide spectrum of diseases. Despite recent advances in our understanding of the cells and circuits implicated in the processing of itch information, chronic itch often presents itself without apparent cause. Here, we identify a spinal subpopulation of inhibitory neurons defined by the expression of Ptf1a involved in gating mechanosensory information self-generated during locomotion. These neurons receive tactile and motor input and establish presynaptic inhibitory contacts on mechanosensory afferents. Loss of these neurons leads to increased hairy skin sensitivity and chronic itch, at least partially mediated through the classic GRPR pathway. These findings shed new light on the mechanisms implicated in chronic itch and open novel targets for therapy developments.