Nature Neuroscience
2, 541 - 548 (1999)
doi:10.1038/9195
The tetrodotoxin-resistant sodium channel SNS has a specialized function
in pain pathwaysArmen N. Akopian1, Veronika Souslova1, Steven England1, 2, Kenji Okuse1, Nobukuni Ogata3, Jan Ure4, Andrew Smith4, Bradley J. Kerr5, Steven B. McMahon5, Sue Boyce6, Ray Hill6, Louise C. Stanfa7, Anthony H. Dickenson7
& John N. Wood11
Molecular Nociception Group, Department of Biology,
Medawar Building, University College, London WC1E 6BT
, UK
2
Present address: Pfizer Central Research,
Sandwich, Kent, CT13 9NJ, UK
3
Second Department of Physiology, Faculty of Medicine,
Hiroshima University, Hiroshima 734, Japan
4
Centre for Genome Research, West Mains
Road, Edinburgh EH9 3JQ, UK
5
Department of Physiology, UMDS, St. Thomas Hospital
Medical School, Lambeth Road, London
SE1 7EH, UK
6
Merck Sharp and Dohme Research Labs, Terlings Park
, Harlow, Essex CM20 2QR, UK
7
Department of Pharmacology, University College,
London WC1E 6BT, UK
Correspondence should be addressed to John N. Wood j.wood@ucl.ac.ukMany 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  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.
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