Novel omega-conotoxins from C. catus reverse signs of mouse inflammatory pain after systemic administration

Sadeghi, Mahsa, Murali, Swetha S., Lewis, Richard J., Alewood, Paul F., Mohammadi, Sarasa and Christie, MacDonald J. (2013) Novel omega-conotoxins from C. catus reverse signs of mouse inflammatory pain after systemic administration. Molecular Pain, 9 1: 51.1-51.8. doi:10.1186/1744-8069-9-51


Author Sadeghi, Mahsa
Murali, Swetha S.
Lewis, Richard J.
Alewood, Paul F.
Mohammadi, Sarasa
Christie, MacDonald J.
Title Novel omega-conotoxins from C. catus reverse signs of mouse inflammatory pain after systemic administration
Formatted title
Novel ω-conotoxins from C. catus reverse signs of mouse inflammatory pain after systemic administration
Journal name Molecular Pain   Check publisher's open access policy
ISSN 1744-8069
Publication date 2013-10-20
Year available 2013
Sub-type Article (original research)
DOI 10.1186/1744-8069-9-51
Open Access Status DOI
Volume 9
Issue 1
Start page 51.1
End page 51.8
Total pages 9
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Subject 2703 Anesthesiology and Pain Medicine
1313 Molecular Medicine
2804 Cellular and Molecular Neuroscience
Abstract Background: Antagonists of N-type voltage-gated calcium channels (VGCC), Ca(v)2.2, can manage severe chronic pain with intrathecal use and may be effective systemically. A series of novel omega-conotoxins that selectively inhibit N-type VGCCs was isolated from Conus catus. In the present study, the potency and reversibility of omega-conotoxins CVID, CVIE and CVIF to inhibit N-type calcium currents were investigated in mouse isolated dorsal root ganglion (DRG) neurons. The systemic potency of each omega-conotoxin to reverse signs of mouse chronic inflammatory pain was also compared.
Formatted abstract
Background: Antagonists of N-type voltage-gated calcium channels (VGCC), Cav2.2, can manage severe chronic pain with intrathecal use and may be effective systemically. A series of novel ω-conotoxins that selectively inhibit N-type VGCCs was isolated from Conus catus. In the present study, the potency and reversibility of ω-conotoxins CVID, CVIE and CVIF to inhibit N-type calcium currents were investigated in mouse isolated dorsal root ganglion (DRG) neurons. The systemic potency of each ω-conotoxin to reverse signs of mouse chronic inflammatory pain was also compared.

Results:In DRG neurons, the rank order of potency to inhibit N-type calcium currents was CVIE > CVIF > CVID. After subcutaneous administration, CVID and CVIE, but not CVIF, partially reversed impaired weight bearing in mice injected with Freund's complete adjuvant (CFA) three days prior to testing. No side-effects associated with systemic administration of ω-conotoxins were observed.

Conclusions: The present study indicates a potential for CVID and CVIE to be developed as systemically active analgesics with no accompanying neurological side-effects.
Keyword Calcium channel
Conotoxin
Inflammatory pain
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 512390
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
 
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