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Sci. Signal., 30 November 2010
Vol. 3, Issue 150, p. ec362
[DOI: 10.1126/scisignal.3150ec362]

EDITORS' CHOICE

Neuroscience An Innate Itch?

Elizabeth M. Adler

Science Signaling, AAAS, Washington, DC 20005, USA

Although best known for their role in mediating innate immune responses, Toll-like receptors (TLRs) have also been identified in the nervous system. Noting that innate immune responses have been implicated in hypersensitivity to pain, Liu et al. wondered whether pain sensitivity might be altered in mice lacking the TLR7 receptor (Tlr7–/– mice). Tlr7–/– mice in fact showed normal sensitivity to pain; however, they scratched themselves less than wild-type mice did in response to agents that can induce itch through mechanisms independent of histamine release. Moreover, intradermal injection of TLR7 ligands with antiviral activity, such as imiquimod, induced scratching behavior (more effectively in wild-type than Tlr7–/– mice). Using a combination of immunohistochemistry, in situ hybridization, and single-cell RT-PCR, the authors determined that TLR7 was coexpressed in small-size dorsal root ganglion (DRG) neurons with the capsaicin-sensitive TRPV1 channel, gastrin-related peptide (GRP), and the G protein–coupled receptor MrgprA3 (all of which have been implicated in itch signaling). Indeed, ablation of sensory neurons expressing TRPV1 with resiniferatoxin (a highly potent TRPV1 agonist) virtually eliminated imiquimod-induced scratching, although sensitivity to imiquimod remained intact in mice lacking TRPV1. Patch-clamp analysis indicated that imiquimod elicited inward currents in capsaicin-sensitive DRG neurons from wild-type mice but not those lacking TLR7. The authors thus conclude that TLR7 mediates itch and may represent a target for antipruritic therapy.

T. Liu, Z. Z. Xu, C. K. Park, T. Berta, R. R. Ji, Toll-like receptor 7 mediates pruritus. Nat. Neurosci. 13, 1460–1462 (2010). [PubMed]

Citation: E. M. Adler, An Innate Itch? Sci. Signal. 3, ec362 (2010).



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