Faculty Collaboration Database

Kappa opioids inhibit spinal output neurons to suppress itch. Sci Adv 2024 Sep 27;10(39):eadp6038

Date

09/25/2024

Pubmed ID

39321286

Pubmed Central ID

PMC11423883

DOI

10.1126/sciadv.adp6038

Scopus ID

2-s2.0-85204941573 (requires institutional sign-in at Scopus site)   4 Citations

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 Ca²⁺ 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.

Author List

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

Authors

David Baranger PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Tayler D. Sheahan PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Interneurons
Male
Mice
Morphinans
Neurons
Pruritus
Receptors, Bombesin
Receptors, Opioid, kappa
Spinal Cord
Spiro Compounds