Novel ω-conotoxins from C. catus reverse signs of mouse inflammatory pain after systemic administration
- Equal contributors
1 Discipline of Pharmacology, University of Sydney, Sydney, NSW 2006, Australia
2 Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD 4072, Australia
Molecular Pain 2013, 9:51 doi:10.1186/1744-8069-9-51Published: 20 October 2013
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.
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.
The present study indicates a potential for CVID and CVIE to be developed as systemically active analgesics with no accompanying neurological side-effects.