Intrathecal alpha-conotoxins Vc1.1, AuIB and MII acting on distinct nicotinic receptor subtypes reverse signs of neuropathic pain

Napier, I. A., Klimis, H., Rycroft, B. K., Jin, A. H., Alewood, P. F., Motin, L., Adams, D. J. and Christie, M. J. (2012) Intrathecal alpha-conotoxins Vc1.1, AuIB and MII acting on distinct nicotinic receptor subtypes reverse signs of neuropathic pain. Neuropharmacology, 62 7: 2202-2207. doi:10.1016/j.neuropharm.2012.01.016


Author Napier, I. A.
Klimis, H.
Rycroft, B. K.
Jin, A. H.
Alewood, P. F.
Motin, L.
Adams, D. J.
Christie, M. J.
Title Intrathecal alpha-conotoxins Vc1.1, AuIB and MII acting on distinct nicotinic receptor subtypes reverse signs of neuropathic pain
Journal name Neuropharmacology   Check publisher's open access policy
ISSN 0028-3908
1873-7064
Publication date 2012-06-01
Sub-type Article (original research)
DOI 10.1016/j.neuropharm.2012.01.016
Volume 62
Issue 7
Start page 2202
End page 2207
Total pages 6
Place of publication Oxford, United Kingdom
Publisher Pergamon
Collection year 2013
Language eng
Formatted abstract
The large diversity of peptides from venomous creatures with high affinity for molecules involved in the development and maintenance of neuropathic pain has led to a surge in venom-derived analgesic research. Some members of the α-conotoxin family from Conus snails which specifically target subtypes of nicotinic acetylcholine receptors (nAChR) have been shown to be effective at reducing mechanical allodynia in neuropathic pain models. We sought to determine if three such peptides, Vc1.1, AuIB and MII were effective following intrathecal administration in a rat neuropathic pain model because they exhibit different affinities for the major putative pain relieving targets of α-conotoxins. Intrathecal administration of α-conotoxins, Vc1.1, AuIB and MII into neuropathic rats reduced mechanical allodynia for up to 6 h without significant side effects. In vitro patch-clamp electrophysiology of primary afferent synaptic transmission revealed the mode of action of these toxins was not via a GABA B-dependant mechanism, and is more likely related to their action at nAChRs containing combinations of α3, α7 or other subunits. Intrathecal nAChR subunit-selective conotoxins are therefore promising tools for the effective treatment of neuropathic pain.
Keyword Conotoxin
Pain
Nicotinic
nAChR
Allodynia
Intrathecal
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2013 Collection
Institute for Molecular Bioscience - Publications
 
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