title: Analgesic effect of highly reversible ω-conotoxin FVIA on N type Ca2+ channels.
abstract: BACKGROUND
  N-type Ca2+ channels (Ca(v)2.2) play an important role in the transmission of pain signals to the central nervous system. ω-Conotoxin (CTx)-MVIIA, also called ziconotide (Prialt®), effectively alleviates pain, without causing addiction, by blocking the pores of these channels. Unfortunately, CTx-MVIIA has a narrow therapeutic window and produces serious side effects due to the poor reversibility of its binding to the channel. It would thus be desirable to identify new analgesic blockers with binding characteristics that lead to fewer adverse side effects.
  
  
  RESULTS
  Here we identify a new CTx, FVIA, from the Korean Conus Fulmen and describe its effects on pain responses and blood pressure. The inhibitory effect of CTx-FVIA on N-type Ca2+ channel currents was dose-dependent and similar to that of CTx-MVIIA. However, the two conopeptides exhibited markedly different degrees of reversibility after block. CTx-FVIA effectively and dose-dependently reduced nociceptive behavior in the formalin test and in neuropathic pain models, and reduced mechanical and thermal allodynia in the tail nerve injury rat model. CTx-FVIA (10 ng) also showed significant analgesic effects on writhing in mouse neurotransmitter- and cytokine-induced pain models, though it had no effect on acute thermal pain and interferon-γ induced pain. Interestingly, although both CTx-FVIA and CTx-MVIIA depressed arterial blood pressure immediately after administration, pressure recovered faster and to a greater degree after CTx-FVIA administration.
  
  
  CONCLUSIONS
  The analgesic potency of CTx-FVIA and its greater reversibility could represent advantages over CTx-MVIIA for the treatment of refractory pain and contribute to the design of an analgesic with high potency and low side effects.
authors.affiliation: Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, South Korea.
authors.forename: Seungkyu
authors.initials: S
authors.lastname: Lee
authors.forename: Yoonji
authors.initials: Y
authors.lastname: Kim
authors.forename: Seung Keun
authors.initials: SK
authors.lastname: Back
authors.forename: Hee-Woo
authors.initials: HW
authors.lastname: Choi
authors.forename: Ju Yeon
authors.initials: JY
authors.lastname: Lee
authors.forename: Hyun Ho
authors.initials: HH
authors.lastname: Jung
authors.forename: Jae Ha
authors.initials: JH
authors.lastname: Ryu
authors.forename: Hong-Won
authors.initials: HW
authors.lastname: Suh
authors.forename: Heung Sik
authors.initials: HS
authors.lastname: Na
authors.forename: Hyun Jeong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Hyewhon
authors.initials: H
authors.lastname: Rhim
authors.forename: Jae Il
authors.initials: JI
authors.lastname: Kim
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020864:Calcium Channels, N-Type / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020960:omega-Conotoxins / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D018712:Analgesics, Non-Narcotic; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020960:omega-Conotoxins; C557085:omega-conotoxin-FVIA, Conus fulmen; C078452:ziconotide