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Analgesic effect of highly reversible omega-conotoxin FVIA on N type Ca2+ channels

Cited 23 time in Web of Science Cited 32 time in Scopus
Authors
Lee, Seungkyu; Kim, Yoonji; Back, Seung Keun; Choi, Hee-Woo; Jung, Hyun Ho; Suh, Hong-Won; Kim, Hyun Jeong; Kim, Jae Il; Rhim, Hyewhon; Na, Heung Sik; Ryu, Jae Ha; Lee, Ju Yeon
Issue Date
2010-12-21
Publisher
BIOMED CENTRAL LTD
Citation
MOLECULAR PAIN, Vol.6 :97 (21 December 2010)
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. omega-Conotoxin (CTx)-MVIIA, also called ziconotide (Prialt (R)), 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-gamma 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.
ISSN
1744-8069
Language
English
URI
http://hdl.handle.net/10371/80365
DOI
https://doi.org/10.1186/1744-8069-6-97
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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