title: Novel ω-conotoxins from C. catus reverse signs of mouse inflammatory pain after systemic administration.
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 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.
authors.forename: Mahsa
authors.initials: M
authors.lastname: Sadeghi
authors.forename: Swetha S
authors.initials: SS
authors.lastname: Murali
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lewis
authors.forename: Paul F
authors.initials: PF
authors.lastname: Alewood
authors.forename: Sarasa
authors.initials: S
authors.lastname: Mohammadi
authors.affiliation: Discipline of Pharmacology, University of Sydney, Sydney, NSW 2006, Australia. mac.christie@sydney.edu.au.
authors.forename: MacDonald J
authors.initials: MJ
authors.lastname: Christie
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D020960:omega-Conotoxins / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: C461486:AM336; D000700:Analgesics; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020960:omega-Conotoxins