Presynaptic inhibition of cutaneous afferents prevents self-generated itch

Abstract

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. Methodology: A.E.; Validation: A.E. and R.K.; Formal Analysis: A.E.; Investigation: A.E.; Resources: A.E.; Data Curation: A.E.; Writing-Original Draft: A.E. and R.K.; Writing-Review and Editing: A.E. and R.K.; Visualization: A.E.; Supervision: R.K.; Funding Acquisition: R.K.