A dedicated inhibitory circuit for gating itch in the spinal cord

Le résumé fourni par la source

Various populations of spinal inhibitory neurons have been implicated in itch inhibition, but the precise mechanisms underlying tonic gating of itch and its inhibition by pain remain incompletely understood. Here, we identify a subset of inhibitory interneurons that uniquely express neurokinin receptor 3 (NK3R) in the spinal cord of mice. NK3R neurons receive monosynaptic input from Tac1+ sensory neurons, which release substance P (SP) and project directly to gastrin-releasing peptide receptor (GRPR)-expressing neurons that are dedicated to itch transmission. Silencing of NK3R inhibitory neurons disinhibits GRPR neurons and induces neuropathic itch, whereas their activation profoundly impairs itch but not pain transmission. These findings suggest that spinal NK3R inhibitory neurons serve as a pivotal and specific microcircuit for tonically gating of itch, and that the SP-NK3R-GRPR pathway may underlie the inhibition of itch by pain that activates the primary afferents to release SP onto the spinal cord.

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