Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain

Osteen, Jeremiah D., Herzig, Volker, Gilchrist, John, Emrick, Joshua J., Zhang, Chuchu, Wang, Xidao, Castro, Joel, Garcia-Caraballo, Sonia, Grundy, Luke, Rychkov, Grigori Y., Weyer, Andy D., Dekan, Zoltan, Undheim, Eivind A. B., Alewood, Paul, Stucky, Cheryl L., Brierley, Stuart M., Basbaum, Allan I., Bosmans, Frank, King, Glenn F. and Julius, David (2016) Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain. Nature, 543 7608: 494-499. doi:10.1038/nature17976


Author Osteen, Jeremiah D.
Herzig, Volker
Gilchrist, John
Emrick, Joshua J.
Zhang, Chuchu
Wang, Xidao
Castro, Joel
Garcia-Caraballo, Sonia
Grundy, Luke
Rychkov, Grigori Y.
Weyer, Andy D.
Dekan, Zoltan
Undheim, Eivind A. B.
Alewood, Paul
Stucky, Cheryl L.
Brierley, Stuart M.
Basbaum, Allan I.
Bosmans, Frank
King, Glenn F.
Julius, David
Title Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain
Formatted title
Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
1476-4687
Publication date 2016-06-06
Year available 2016
Sub-type Article (original research)
DOI 10.1038/nature17976
Open Access Status Not Open Access
Volume 543
Issue 7608
Start page 494
End page 499
Total pages 6
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted abstract
Voltage-gated sodium (Nav) channels initiate action potentials in most neurons, including primary afferent nerve fibres of the pain pathway. Local anaesthetics block pain through non-specific actions at all Nav channels, but the discovery of selective modulators would facilitate the analysis of individual subtypes of these channels and their contributions to chemical, mechanical, or thermal pain. Here we identify and characterize spider (Heteroscodra maculata) toxins that selectively activate the Nav1.1 subtype, the role of which in nociception and pain has not been elucidated. We use these probes to show that Nav1.1-expressing fibres are modality-specific nociceptors: their activation elicits robust pain behaviours without neurogenic inflammation and produces profound hypersensitivity to mechanical, but not thermal, stimuli. In the gut, high-threshold mechanosensitive fibres also express Nav1.1 and show enhanced toxin sensitivity in a mouse model of irritable bowel syndrome. Together, these findings establish an unexpected role for Nav1.1 channels in regulating the excitability of sensory nerve fibres that mediate mechanical pain.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
 
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Created: Fri, 17 Jun 2016, 21:02:00 EST by Susan Allen on behalf of Institute for Molecular Bioscience