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

(2016) NATURE. 534(7608). p.494-499
Author
Organization
Abstract
Voltage-gated sodium (Na-v) 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 Na-v 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 Na(v)1.1 subtype, the role of which in nociception and pain has not been elucidated. We use these probes to show that Na(v)1.1-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 Na(v)1.1 and show enhanced toxin sensitivity in a mouse model of irritable bowel syndrome. Together, these findings establish an unexpected role for Na(v)1.1 channels in regulating the excitability of sensory nerve fibres that mediate mechanical pain.
Keywords
GATED SODIUM-CHANNELS, RAT DORSAL-ROOT, VOLTAGE-SENSOR, NEUROPATHIC PAIN, ANTIEPILEPTIC DRUGS, GANGLION NEURONS, RECEPTOR, EXPRESSION, MIGRAINE, MUTATIONS

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Chicago
Osteen, Jeremiah D, Volker Herzig, John Gilchrist, Joshua J Emrick, Chuchu Zhang, Xidao Wang, Joel Castro, et al. 2016. “Selective Spider Toxins Reveal a Role for the Nav1.1 Channel in Mechanical Pain.” Nature 534 (7608): 494–499.
APA
Osteen, Jeremiah D, Herzig, V., Gilchrist, J., Emrick, J. J., Zhang, C., Wang, X., Castro, J., et al. (2016). Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain. NATURE, 534(7608), 494–499.
Vancouver
1.
Osteen JD, Herzig V, Gilchrist J, Emrick JJ, Zhang C, Wang X, et al. Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain. NATURE. 2016;534(7608):494–9.
MLA
Osteen, Jeremiah D, Volker Herzig, John Gilchrist, et al. “Selective Spider Toxins Reveal a Role for the Nav1.1 Channel in Mechanical Pain.” NATURE 534.7608 (2016): 494–499. Print.
@article{8584510,
  abstract     = {Voltage-gated sodium (Na-v) 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 Na-v 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 Na(v)1.1 subtype, the role of which in nociception and pain has not been elucidated. We use these probes to show that Na(v)1.1-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 Na(v)1.1 and show enhanced toxin sensitivity in a mouse model of irritable bowel syndrome. Together, these findings establish an unexpected role for Na(v)1.1 channels in regulating the excitability of sensory nerve fibres that mediate mechanical pain.},
  author       = {Osteen, Jeremiah D and Herzig, Volker and Gilchrist, John and Emrick, Joshua J and Zhang, Chuchu and Wang, Xidao and Castro, Joel and Garcia-Caraballo, Sonia and Grundy, Luke and Rychkov, Grigori Y and Weyer, Andy D and Dekan, Zoltan and Undheim, Eivind AB and Alewood, Paul and Stucky, Cheryl L and Brierley, Stuart M and Basbaum, Allan I and Bosmans, Frank and King, Glenn F and Julius, David},
  issn         = {0028-0836},
  journal      = {NATURE},
  language     = {eng},
  number       = {7608},
  pages        = {494--499},
  title        = {Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain},
  url          = {http://dx.doi.org/10.1038/nature17976},
  volume       = {534},
  year         = {2016},
}

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