Identification of a convergent spinal neuron population that encodes itch. bioRxiv 2023 Nov 08
Date
10/24/2023Pubmed ID
37873278Pubmed Central ID
PMC10592866DOI
10.1101/2023.09.29.560205Abstract
Itch is a protective sensation that drives scratching. Although specific cell types have been proposed to underlie itch, the neural circuit basis for itch remains unclear. Here, we used two-photon Ca2+ imaging of the dorsal horn to visualize the neuronal populations that are activated by itch-inducing agents. We identify a convergent population of spinal neurons that is defined by the expression of GRPR. Moreover, we discover that itch is conveyed to the brain via GRPR-expressing spinal output neurons that target the lateral parabrachial nucleus. Further, we show that nalfurafine, a clinically effective kappa opioid receptor agonist, relieves itch by inhibiting GRPR spinoparabrachial neurons. Finally, we demonstrate that a subset of GRPR spinal neurons show persistent, cell-intrinsic Ca2+ oscillations. These experiments provide the first 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 SEAuthors
David Baranger PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of WisconsinTayler D. Sheahan PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
