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

TitleThe tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways.
Publication TypeJournal Article
Year of Publication1999
AuthorsAkopian AN, Souslova V, England S, Okuse K, Ogata N, Ure J, Smith A, Kerr BJ, McMahon SB, Boyce S, Hill R, Stanfa LC, Dickenson AH, Wood JN
JournalNat Neurosci
Volume2
Issue6
Pagination541-8
Date Published1999 Jun
ISSN1097-6256
KeywordsAfferent Pathways, Animals, Behavior, Animal, Differential Threshold, Drug Resistance, Electric Conductivity, Electric Stimulation, Mice, Mice, Inbred C57BL, Mice, Knockout, NAV1.8 Voltage-Gated Sodium Channel, Nerve Fibers, Neurons, Afferent, Nociceptors, Pain, Pain Threshold, Physical Stimulation, Sodium Channels, Tetrodotoxin
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 alpha 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.

DOI10.1038/9195
Alternate JournalNat. Neurosci.
PubMed ID10448219
Grant List / / Wellcome Trust / United Kingdom