PMID- 10448219
OWN - NLM
STAT- MEDLINE
DCOM- 19990902
LR  - 20121115
IS  - 1097-6256 (Print)
IS  - 1097-6256 (Linking)
VI  - 2
IP  - 6
DP  - 1999 Jun
TI  - The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain 
      pathways.
PG  - 541-8
AB  - 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.
FAU - Akopian, A N
AU  - Akopian AN
AD  - Molecular Nociception Group, Department of Biology, Medawar Building, University 
      College, London WC1E 6BT, UK.
FAU - Souslova, V
AU  - Souslova V
FAU - England, S
AU  - England S
FAU - Okuse, K
AU  - Okuse K
FAU - Ogata, N
AU  - Ogata N
FAU - Ure, J
AU  - Ure J
FAU - Smith, A
AU  - Smith A
FAU - Kerr, B J
AU  - Kerr BJ
FAU - McMahon, S B
AU  - McMahon SB
FAU - Boyce, S
AU  - Boyce S
FAU - Hill, R
AU  - Hill R
FAU - Stanfa, L C
AU  - Stanfa LC
FAU - Dickenson, A H
AU  - Dickenson AH
FAU - Wood, J N
AU  - Wood JN
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Neurosci
JT  - Nature neuroscience
JID - 9809671
RN  - 0 (NAV1.8 Voltage-Gated Sodium Channel)
RN  - 0 (Scn10a protein, mouse)
RN  - 0 (Sodium Channels)
RN  - 4368-28-9 (Tetrodotoxin)
SB  - IM
MH  - Afferent Pathways/physiology
MH  - Animals
MH  - Behavior, Animal/physiology
MH  - Differential Threshold/physiology
MH  - Drug Resistance
MH  - Electric Conductivity
MH  - Electric Stimulation
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout/genetics
MH  - NAV1.8 Voltage-Gated Sodium Channel
MH  - Nerve Fibers/physiology
MH  - Neurons, Afferent/physiology
MH  - Nociceptors/physiology
MH  - Pain/*physiopathology
MH  - Pain Threshold/physiology
MH  - Physical Stimulation
MH  - Sodium Channels/*drug effects/genetics/*physiology
MH  - Tetrodotoxin/*pharmacology
EDAT- 1999/08/17 10:00
MHDA- 2001/03/23 10:01
CRDT- 1999/08/17 10:00
PHST- 1999/08/17 10:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/08/17 10:00 [entrez]
AID - 10.1038/9195 [doi]
PST - ppublish
SO  - Nat Neurosci. 1999 Jun;2(6):541-8. doi: 10.1038/9195.