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

Jeremiah D. Osteen, Volker Herzig, John Gilchrist, Joshua J. Emrick, Chuchu Zhang, Xidao Wang, Joel Castro, Sonia Garcia-Caraballo, Luke Grundy, Grigori Y. Rychkov, Andy D. Weyer, Zoltan Dekan, Eivind A. B. Undheim, Paul Alewood, Cheryl L. Stucky, Stuart M. Brierley, Allan I. Basbaum, Frank Bosmans (), Glenn F. King () and David Julius ()
Additional contact information
Jeremiah D. Osteen: University of California
Volker Herzig: Institute for Molecular Bioscience, University of Queensland
John Gilchrist: Johns Hopkins University School of Medicine
Joshua J. Emrick: University of California
Chuchu Zhang: University of California
Xidao Wang: University of California
Joel Castro: Visceral Pain Group, Flinders University, Bedford Park
Sonia Garcia-Caraballo: Visceral Pain Group, Flinders University, Bedford Park
Luke Grundy: Visceral Pain Group, Flinders University, Bedford Park
Grigori Y. Rychkov: Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine, University of Adelaide, South Australian Health and Medical Research Institute (SAHMRI), North Terrace
Andy D. Weyer: Neurobiology, and Anatomy, Medical College of Wisconsin
Zoltan Dekan: Institute for Molecular Bioscience, University of Queensland
Eivind A. B. Undheim: Institute for Molecular Bioscience, University of Queensland
Paul Alewood: Institute for Molecular Bioscience, University of Queensland
Cheryl L. Stucky: Neurobiology, and Anatomy, Medical College of Wisconsin
Stuart M. Brierley: Visceral Pain Group, Flinders University, Bedford Park
Allan I. Basbaum: University of California
Frank Bosmans: Johns Hopkins University School of Medicine
Glenn F. King: Institute for Molecular Bioscience, University of Queensland
David Julius: University of California

Nature, 2016, vol. 534, issue 7608, 494-499

Abstract: 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.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature17976 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:534:y:2016:i:7608:d:10.1038_nature17976

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature17976

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().