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PMID: 12060708 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A role for ASIC3 in the modulation of high-intensity pain stimuli.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 13 ·2002-06-25 ·Pages 8992-7

Chen CC, Zimmer A, Sun WH, Hall J, Brownstein MJ, Zimmer A

Abstract

Acid-sensing ion channel 3 (ASIC3), a proton-gated ion channel of the degenerins/epithelial sodium channel (DEG/ENaC) receptor family is expressed predominantly in sensory neurons including nociceptive neurons responding to protons. To study the role of ASIC3 in pain signaling, we generated ASIC3 knockout mice. Mutant animals were healthy and responded normally to most sensory stimuli. However, in behavioral assays for pain responses, ASIC3 null mutant mice displayed a reduced latency to the onset of pain responses, or more pain-related behaviors, when stimuli of moderate to high intensity were used. This unexpected effect seemed independent of the modality of the stimulus and was observed in the acetic acid-induced writhing test (0.6 vs. 0.1-0.5%), in the hot-plate test (52.5 and 55 vs. 50 degrees C), and in tests for mechanically induced pain (tail-pinch vs. von Frey filaments). We postulate that ASIC3 is involved in modulating moderate- to high-intensity pain sensation.

MeSH Terms
Acid Sensing Ion Channels Animals Base Sequence Behavior, Animal DNA Primers Membrane Proteins Mice Mice, Knockout Nerve Tissue Proteins Pain/physiopathology Physical Stimulation Sodium Channels/genetics,physiology
Chemicals
ASIC3 protein, human Acid Sensing Ion Channels DNA Primers Membrane Proteins Nerve Tissue Proteins Sodium Channels
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Chen Chih-Cheng
Laboratory of Genetics, National Institute of Mental Health, 36 Convent Drive 3D06, Bethesda, MD 20892, USA.
Zimmer Anne
Sun Wei-Hsin
Hall Jennifer
Brownstein Michael J
Zimmer Andreas
References (29)
29 references, click to expand
  1. Impaired nociception and pain sensation in mice lacking the capsaicin receptor.
    Science. 2000 Apr 14;288(5464):306-13 PMID: 10764638
  2. DEG/ENaC channels: a touchy superfamily that watches its salt.
    Bioessays. 1999 Jul;21(7):568-78 PMID: 10472184
  3. The mammalian sodium channel BNC1 is required for normal touch sensation.
    Nature. 2000 Oct 26;407(6807):1007-11 PMID: 11069180
  4. Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons.
    Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):711-6 PMID: 11120882
  5. The vanilloid receptor: a molecular gateway to the pain pathway.
    Annu Rev Neurosci. 2001;24:487-517 PMID: 11283319
  6. Single-channel properties of recombinant acid-sensitive ion channels formed by the subunits ASIC2 and ASIC3 from dorsal root ganglion neurons expressed in Xenopus oocytes.
    J Gen Physiol. 2001 Jun;117(6):563-72 PMID: 11382806
  7. Increased acid-sensing ion channel ASIC-3 in inflamed human intestine.
    Eur J Gastroenterol Hepatol. 2001 Aug;13(8):891-6 PMID: 11507351
  8. Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors.
    J Neurosci. 2001 Oct 15;21(20):8026-33 PMID: 11588175
  9. The DRASIC cation channel contributes to the detection of cutaneous touch and acid stimuli in mice.
    Neuron. 2001 Dec 20;32(6):1071-83 PMID: 11754838
  10. Pain mechanisms: a new theory.
    Science. 1965 Nov 19;150(3699):971-9 PMID: 5320816
  11. Protons selectively induce lasting excitation and sensitization to mechanical stimulation of nociceptors in rat skin, in vitro.
    J Neurosci. 1992 Jan;12(1):86-95 PMID: 1309578
  12. Manipulating the genome by homologous recombination in embryonic stem cells.
    Annu Rev Neurosci. 1992;15:115-37 PMID: 1575439
  13. Gene interactions affecting mechanosensory transduction in Caenorhabditis elegans.
    Nature. 1994 Feb 3;367(6462):467-70 PMID: 7509039
  14. A transmembrane domain of the putative channel subunit MEC-4 influences mechanotransduction and neurodegeneration in C. elegans.
    Nature. 1994 Feb 3;367(6462):470-3 PMID: 8107806
  15. Pain: past, present and future.
    Can J Exp Psychol. 1993 Dec;47(4):615-29 PMID: 8124287
  16. Decreased activity of spontaneous and noxiously evoked dorsal horn cells during transcutaneous electrical nerve stimulation (TENS).
    Pain. 1994 Sep;58(3):309-15 PMID: 7838579
  17. Pain responses, anxiety and aggression in mice deficient in pre-proenkephalin.
    Nature. 1996 Oct 10;383(6600):535-8 PMID: 8849726
  18. BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels related to degenerins and epithelial sodium channels.
    Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1459-64 PMID: 9037075
  19. A proton-gated cation channel involved in acid-sensing.
    Nature. 1997 Mar 13;386(6621):173-7 PMID: 9062189
  20. Molecular cloning of a non-inactivating proton-gated Na+ channel specific for sensory neurons.
    J Biol Chem. 1997 Aug 22;272(34):20975-8 PMID: 9261094
  21. The acid-sensitive ionic channel subunit ASIC and the mammalian degenerin MDEG form a heteromultimeric H+-gated Na+ channel with novel properties.
    J Biol Chem. 1997 Nov 14;272(46):28819-22 PMID: 9360943
  22. A modulatory subunit of acid sensing ion channels in brain and dorsal root ganglion cells.
    J Biol Chem. 1997 Nov 21;272(47):29778-83 PMID: 9368048
  23. Hypoalgesia in mice with a targeted deletion of the tachykinin 1 gene.
    Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2630-5 PMID: 9482938
  24. H(+)-gated cation channels: neuronal acid sensors in the NaC/DEG family of ion channels.
    Curr Opin Neurobiol. 1998 Jun;8(3):418-24 PMID: 9687356
  25. A sensory neuron-specific, proton-gated ion channel.
    Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10240-5 PMID: 9707631
  26. Identification, functional expression and chromosomal localisation of a sustained human proton-gated cation channel.
    FEBS Lett. 1998 Aug 21;433(3):257-60 PMID: 9744806
  27. Heritability of nociception I: responses of 11 inbred mouse strains on 12 measures of nociception.
    Pain. 1999 Mar;80(1-2):67-82 PMID: 10204719
  28. H(+)-gated cation channels.
    Ann N Y Acad Sci. 1999 Apr 30;868:67-76 PMID: 10414282
  29. A new member of the acid-sensing ion channel family.
    Neuroreport. 2000 Jul 14;11(10):2217-22 PMID: 10923674
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.122245999
Published
2002-06-25
Epub
2002-00-11
Pages
8992-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC124411
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.122245999 PMC Full Text View journal details
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