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Analgesic effect of highly reversible ω-conotoxin FVIA on N type Ca(2+ )channels

BACKGROUND: N-type Ca(2+ )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. Unfort...

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Autores principales: Lee, Seungkyu, Kim, Yoonji, Back, Seung Keun, Choi, Hee-Woo, Lee, Ju Yeon, Jung, Hyun Ho, Ryu, Jae Ha, Suh, Hong-Won, Na, Heung Sik, Kim, Hyun Jeong, Rhim, Hyewhon, Kim, Jae Il
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025903/
https://www.ncbi.nlm.nih.gov/pubmed/21172037
http://dx.doi.org/10.1186/1744-8069-6-97
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author Lee, Seungkyu
Kim, Yoonji
Back, Seung Keun
Choi, Hee-Woo
Lee, Ju Yeon
Jung, Hyun Ho
Ryu, Jae Ha
Suh, Hong-Won
Na, Heung Sik
Kim, Hyun Jeong
Rhim, Hyewhon
Kim, Jae Il
author_facet Lee, Seungkyu
Kim, Yoonji
Back, Seung Keun
Choi, Hee-Woo
Lee, Ju Yeon
Jung, Hyun Ho
Ryu, Jae Ha
Suh, Hong-Won
Na, Heung Sik
Kim, Hyun Jeong
Rhim, Hyewhon
Kim, Jae Il
author_sort Lee, Seungkyu
collection PubMed
description BACKGROUND: N-type Ca(2+ )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 Ca(2+ )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.
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spelling pubmed-30259032011-01-25 Analgesic effect of highly reversible ω-conotoxin FVIA on N type Ca(2+ )channels Lee, Seungkyu Kim, Yoonji Back, Seung Keun Choi, Hee-Woo Lee, Ju Yeon Jung, Hyun Ho Ryu, Jae Ha Suh, Hong-Won Na, Heung Sik Kim, Hyun Jeong Rhim, Hyewhon Kim, Jae Il Mol Pain Research BACKGROUND: N-type Ca(2+ )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 Ca(2+ )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. BioMed Central 2010-12-21 /pmc/articles/PMC3025903/ /pubmed/21172037 http://dx.doi.org/10.1186/1744-8069-6-97 Text en Copyright ©2010 Lee et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<url>http://creativecommons.org/licenses/by/2.0</url>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Lee, Seungkyu
Kim, Yoonji
Back, Seung Keun
Choi, Hee-Woo
Lee, Ju Yeon
Jung, Hyun Ho
Ryu, Jae Ha
Suh, Hong-Won
Na, Heung Sik
Kim, Hyun Jeong
Rhim, Hyewhon
Kim, Jae Il
Analgesic effect of highly reversible ω-conotoxin FVIA on N type Ca(2+ )channels
title Analgesic effect of highly reversible ω-conotoxin FVIA on N type Ca(2+ )channels
title_full Analgesic effect of highly reversible ω-conotoxin FVIA on N type Ca(2+ )channels
title_fullStr Analgesic effect of highly reversible ω-conotoxin FVIA on N type Ca(2+ )channels
title_full_unstemmed Analgesic effect of highly reversible ω-conotoxin FVIA on N type Ca(2+ )channels
title_short Analgesic effect of highly reversible ω-conotoxin FVIA on N type Ca(2+ )channels
title_sort analgesic effect of highly reversible ω-conotoxin fvia on n type ca(2+ )channels
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025903/
https://www.ncbi.nlm.nih.gov/pubmed/21172037
http://dx.doi.org/10.1186/1744-8069-6-97
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