Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2006 Nov 07;10345:17030-5. doi: 10.1073/pnas.0601819103.
Show Gene links
Show Anatomy links
muO-conotoxin MrVIB selectively blocks Nav1.8 sensory neuron specific sodium channels and chronic pain behavior without motor deficits.
Ekberg J
,
Jayamanne A
,
Vaughan CW
,
Aslan S
,
Thomas L
,
Mould J
,
Drinkwater R
,
Baker MD
,
Abrahamsen B
,
Wood JN
,
Adams DJ
,
Christie MJ
,
Lewis RJ
.
???displayArticle.abstract???
The tetrodotoxin-resistant voltage-gated sodium channel (VGSC) Na(v)1.8 is expressed predominantly by damage-sensing primary afferent nerves and is important for the development and maintenance of persistent pain states. Here we demonstrate that muO-conotoxin MrVIB from Conus marmoreus displays substantial selectivity for Na(v)1.8 and inhibits pain behavior in models of persistent pain. In rat sensory neurons, submicromolar concentrations of MrVIB blocked tetrodotoxin-resistant current characteristic of Na(v)1.8 but not Na(v)1.9 or tetrodotoxin-sensitive VGSC currents. MrVIB blocked human Na(v)1.8 expressed in Xenopus oocytes with selectivity at least 10-fold greater than other VGSCs. In neuropathic and chronic inflammatory pain models, allodynia and hyperalgesia were both reduced by intrathecal infusion of MrVIB (0.03-3 nmol), whereas motor side effects occurred only at 30-fold higher doses. In contrast, the nonselective VGSC blocker lignocaine displayed no selectivity for allodynia and hyperalgesia versus motor side effects. The actions of MrVIB reveal that VGSC antagonists displaying selectivity toward Na(v)1.8 can alleviate chronic pain behavior with a greater therapeutic index than nonselective antagonists.
Akopian,
The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways.
1999, Pubmed
Akopian,
The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways.
1999,
Pubmed
Akopian,
A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons.
1996,
Pubmed
,
Xenbase
Baker,
Involvement of Na+ channels in pain pathways.
2001,
Pubmed
Bucknill,
Nerve fibers in lumbar spine structures and injured spinal roots express the sensory neuron-specific sodium channels SNS/PN3 and NaN/SNS2.
2002,
Pubmed
Bulaj,
Synthetic muO-conotoxin MrVIB blocks TTX-resistant sodium channel NaV1.8 and has a long-lasting analgesic activity.
2006,
Pubmed
Carr,
The effects of polarizing current on nerve terminal impulses recorded from polymodal and cold receptors in the guinea-pig cornea.
2002,
Pubmed
Chaplan,
Quantitative assessment of tactile allodynia in the rat paw.
1994,
Pubmed
Coggeshall,
Differential expression of tetrodotoxin-resistant sodium channels Nav1.8 and Nav1.9 in normal and inflamed rats.
2004,
Pubmed
Daly,
Structures of muO-conotoxins from Conus marmoreus. I nhibitors of tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels in mammalian sensory neurons.
2004,
Pubmed
Dib-Hajj,
NaN, a novel voltage-gated Na channel, is expressed preferentially in peripheral sensory neurons and down-regulated after axotomy.
1998,
Pubmed
Djouhri,
The TTX-resistant sodium channel Nav1.8 (SNS/PN3): expression and correlation with membrane properties in rat nociceptive primary afferent neurons.
2003,
Pubmed
Fainzilber,
A new conotoxin affecting sodium current inactivation interacts with the delta-conotoxin receptor site.
1995,
Pubmed
Gold,
Redistribution of Na(V)1.8 in uninjured axons enables neuropathic pain.
2003,
Pubmed
Kerr,
A role for the TTX-resistant sodium channel Nav 1.8 in NGF-induced hyperalgesia, but not neuropathic pain.
2001,
Pubmed
Khasar,
A tetrodotoxin-resistant sodium current mediates inflammatory pain in the rat.
1998,
Pubmed
Kim,
The changes in expression of three subtypes of TTX sensitive sodium channels in sensory neurons after spinal nerve ligation.
2001,
Pubmed
Lai,
Inhibition of neuropathic pain by decreased expression of the tetrodotoxin-resistant sodium channel, NaV1.8.
2002,
Pubmed
Lai,
Voltage-gated sodium channels and hyperalgesia.
2004,
Pubmed
Leipold,
Molecular interaction of delta-conotoxins with voltage-gated sodium channels.
2005,
Pubmed
Lewis,
Therapeutic potential of venom peptides.
2003,
Pubmed
Nassar,
Nociceptor-specific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain.
2004,
Pubmed
Nassar,
Neuropathic pain develops normally in mice lacking both Na(v)1.7 and Na(v)1.8.
2005,
Pubmed
Okuse,
Annexin II light chain regulates sensory neuron-specific sodium channel expression.
2002,
Pubmed
Renganathan,
Contribution of Na(v)1.8 sodium channels to action potential electrogenesis in DRG neurons.
2001,
Pubmed
Roza,
The tetrodotoxin-resistant Na+ channel Nav1.8 is essential for the expression of spontaneous activity in damaged sensory axons of mice.
2003,
Pubmed
Seltzer,
A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury.
1990,
Pubmed
Smith,
The novel N-type calcium channel blocker, AM336, produces potent dose-dependent antinociception after intrathecal dosing in rats and inhibits substance P release in rat spinal cord slices.
2002,
Pubmed
Strassman,
Electrophysiological evidence for tetrodotoxin-resistant sodium channels in slowly conducting dural sensory fibers.
1999,
Pubmed
West,
Effects of delta-conotoxins PVIA and SVIE on sodium channels in the amphibian sympathetic nervous system.
2005,
Pubmed
Yiangou,
SNS/PN3 and SNS2/NaN sodium channel-like immunoreactivity in human adult and neonate injured sensory nerves.
2000,
Pubmed
Yoshimura,
The involvement of the tetrodotoxin-resistant sodium channel Na(v)1.8 (PN3/SNS) in a rat model of visceral pain.
2001,
Pubmed
Zhang,
NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels.
2005,
Pubmed
Zhang,
Ceramide, a putative second messenger for nerve growth factor, modulates the TTX-resistant Na(+) current and delayed rectifier K(+) current in rat sensory neurons.
2002,
Pubmed
Zorn,
The muO-conotoxin MrVIA inhibits voltage-gated sodium channels by associating with domain-3.
2006,
Pubmed
