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Papers of the Week


Papers: 21 Sep 2024 - 27 Sep 2024


2024 Sep 27


Sci Adv


39321286


10


39

Editor's Pick

Kappa opioids inhibit spinal output neurons to suppress itch.

Authors

Sheahan TD, Warwick CA, Cui AY, Baranger DAA, Perry VJ, Smith KM, Manalo AP, Nguyen EK, Koerber HR, Ross SE

Abstract

Itch is a protective sensation that drives scratching. Although specific cell types have been proposed to underlie itch, the neural basis for itch remains unclear. Here, we used two-photon Ca imaging of the dorsal horn to visualize neuronal populations that are activated by itch-inducing agents. We identify a convergent population of spinal interneurons recruited by diverse itch-causing stimuli that represents a subset of neurons that express the gastrin-releasing peptide receptor (GRPR). Moreover, we find that itch is conveyed to the brain via GRPR-expressing spinal output neurons that target the lateral parabrachial nuclei. We then show that the kappa opioid receptor agonist nalfurafine relieves itch by selectively inhibiting GRPR spinoparabrachial neurons. These experiments provide a population-level view of the spinal neurons that respond to pruritic stimuli, pinpoint the output neurons that convey itch to the brain, and identify the cellular target of kappa opioid receptor agonists for the inhibition of itch.