The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways

Armen N. Akopian, Veronika Souslova, Steven England, Kenji Okuse, Nobukuni Ogata, Jan Ure, Andrew Smith, Bradley J. Kerr, Steven B. McMahon, Sue Boyce, Ray Hill, Louise C. Stanfa, Anthony H. Dickenson, John N. Wood

Research output: Contribution to journalArticlepeer-review

665 Scopus citations

Abstract

Many damage-sensing neurons express tetrodotoxin (TTX)-resistant voltage-gated sodium channels. Here we examined the role of the sensory- neuron-specific (SNS) TTX-resistant sodium channel α subunit in nociception and pain by constructing sns-null mutant mice. These mice expressed only TTX- sensitive sodium currents on step depolarizations from normal resting potentials, showing that all slow TTX-resistant currents are encoded by the sns gene. Null mutants were viable, fertile and apparently normal, although lowered thresholds of electrical activation of C-fibers and increased current densities of TTX-sensitive channels demonstrated compensatory upregulation of TTX-sensitive currents in sensory neurons. Behavioral studies demonstrated a pronounced analgesia to noxious mechanical stimuli, small deficits in noxious thermoreception and delayed development of inflammatory hyperalgesia. These data show that SNS is involved in pain pathways and suggest that blockade of SNS expression or function may produce analgesia without side effects.

Original languageEnglish (US)
Pages (from-to)541-548
Number of pages8
JournalNature Neuroscience
Volume2
Issue number6
DOIs
StatePublished - Jun 1999
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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