Activity-dependent silencing reveals functionally distinct itch-generating sensory neurons

David P. Roberson, Sagi Gudes, Jared M. Sprague, Haley A.W. Patoski, Victoria K. Robson, Felix Blasl, Bo Duan, Seog Bae Oh, Bruce P. Bean, Qiufu Ma, Alexander M. Binshtok, Clifford J. Woolf*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

Abstract

The peripheral terminals of primary sensory neurons detect histamine and non-histamine itch-provoking ligands through molecularly distinct transduction mechanisms. It remains unclear, however, whether these distinct pruritogens activate the same or different afferent fibers. Using a strategy of reversibly silencing specific subsets of murine pruritogen-sensitive sensory axons by targeted delivery of a charged sodium-channel blocker, we found that functional blockade of histamine itch did not affect the itch evoked by chloroquine or SLIGRL-NH2, and vice versa. Notably, blocking itch-generating fibers did not reduce pain-associated behavior. However, silencing TRPV1+ or TRPA1+ neurons allowed allyl isothiocyanate or capsaicin, respectively, to evoke itch, implying that certain peripheral afferents may normally indirectly inhibit algogens from eliciting itch. These findings support the presence of functionally distinct sets of itch-generating neurons and suggest that targeted silencing of activated sensory fibers may represent a clinically useful anti-pruritic therapeutic approach for histaminergic and non-histaminergic pruritus.

Original languageAmerican English
Pages (from-to)910-918
Number of pages9
JournalNature Neuroscience
Volume16
Issue number7
DOIs
StatePublished - Jul 2013

Bibliographical note

Funding Information:
We thank N. Ghasemlou and S. Ross for discussion and O. Viramontes for technical assistance. This study was supported by the US National Institutes of Health (NS072040 to B.P.B., Q.M., B.D. and C.J.W.; NS047710 to B.D. and Q.M.).

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