Analgesic effects of Phα1β toxin: a review of mechanisms of action involving pain pathways
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | https://doi.org/10.1590/1678-9199-JVATITD-2021-0001 http://hdl.handle.net/1843/56258 https://orcid.org/0000-0002-2906-517X https://orcid.org/0000-0003-0603-0342 https://orcid.org/0000-0003-0795-5320 https://orcid.org/0000-0002-3496-6749 https://orcid.org/0000-0002-6832-2765 https://orcid.org/0000-0002-9175-5761 https://orcid.org/0000-0002-0063-4471 https://orcid.org/0000-0002-9562-0602 https://orcid.org/0000-0002-6082-930X |
Resumo: | Phα1β is a neurotoxin purified from spider venom that acts as a high-voltage-activated (HVA) calcium channel blocker. This spider peptide has shown a high selectivity for N-type HVA calcium channels (NVACC) and an analgesic effect in several animal models of pain. Its activity was associated with a reduction in calcium transients, glutamate release, and reactive oxygen species production from the spinal cord tissue and dorsal ganglia root (DRG) in rats and mice. It has been reported that intrathecal (i.t.) administration of Phα1β to treat chronic pain reverted opioid tolerance with a safer profile than ω-conotoxin MVIIA, a highly selective NVACC blocker. Following a recent development of recombinant Phα1β (CTK 01512-2), a new molecular target, TRPA1, the structural arrangement of disulphide bridges, and an effect on glial plasticity have been identified. CTK 01512-2 reproduced the antinociceptive effects of the native toxin not only after the intrathecal but also after the intravenous administration. Herein, we review the Phα1β antinociceptive activity in the most relevant pain models and its mechanisms of action, highlighting the impact of CTK 01512-2 synthesis and its potential for multimodal analgesia. |
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2023-07-14T19:35:34Z2023-07-14T19:35:34Z2021-11-2227https://doi.org/10.1590/1678-9199-JVATITD-2021-00011678-9199http://hdl.handle.net/1843/56258https://orcid.org/0000-0002-2906-517Xhttps://orcid.org/0000-0003-0603-0342https://orcid.org/0000-0003-0795-5320https://orcid.org/0000-0002-3496-6749https://orcid.org/0000-0002-6832-2765https://orcid.org/0000-0002-9175-5761https://orcid.org/0000-0002-0063-4471https://orcid.org/0000-0002-9562-0602https://orcid.org/0000-0002-6082-930XPhα1β is a neurotoxin purified from spider venom that acts as a high-voltage-activated (HVA) calcium channel blocker. This spider peptide has shown a high selectivity for N-type HVA calcium channels (NVACC) and an analgesic effect in several animal models of pain. Its activity was associated with a reduction in calcium transients, glutamate release, and reactive oxygen species production from the spinal cord tissue and dorsal ganglia root (DRG) in rats and mice. It has been reported that intrathecal (i.t.) administration of Phα1β to treat chronic pain reverted opioid tolerance with a safer profile than ω-conotoxin MVIIA, a highly selective NVACC blocker. Following a recent development of recombinant Phα1β (CTK 01512-2), a new molecular target, TRPA1, the structural arrangement of disulphide bridges, and an effect on glial plasticity have been identified. CTK 01512-2 reproduced the antinociceptive effects of the native toxin not only after the intrathecal but also after the intravenous administration. Herein, we review the Phα1β antinociceptive activity in the most relevant pain models and its mechanisms of action, highlighting the impact of CTK 01512-2 synthesis and its potential for multimodal analgesia.Phα1β é uma neurotoxina purificada do veneno de aranha que atua como um bloqueador de canal de cálcio ativado por alta voltagem (HVA). Este peptídeo de aranha mostrou alta seletividade para canais de cálcio HVA tipo N (NVACC) e efeito analgésico em vários modelos animais de dor. Sua atividade foi associada a uma redução nos transientes de cálcio, liberação de glutamato e produção de espécies reativas de oxigênio a partir do tecido da medula espinhal e da raiz dos gânglios dorsais (DRG) em ratos e camundongos. Foi relatado que a administração intratecal (i.t.) de Phα1β para tratar a dor crônica reverteu a tolerância a opioides com um perfil mais seguro do que a ω-conotoxina MVIIA, um bloqueador NVACC altamente seletivo. Após um desenvolvimento recente de Phα1β recombinante (CTK 01512-2), um novo alvo molecular, TRPA1, o arranjo estrutural das pontes dissulfeto e um efeito na plasticidade glial foram identificados. CTK 01512-2 reproduziu os efeitos antinociceptivos da toxina nativa não apenas após a administração intratecal, mas também após a administração intravenosa. Aqui, revisamos a atividade antinociceptiva de Phα1β nos modelos de dor mais relevantes e seus mecanismos de ação, destacando o impacto da síntese de CTK 01512-2 e seu potencial para analgesia multimodal.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas GeraisCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorOutra AgênciaengUniversidade Federal de Minas GeraisUFMGBrasilICB - DEPARTAMENTO DE FARMACOLOGIAJournal of Venomous Animals and Toxins including Tropical DiseasesDorAnalgesiaAnalgésicosNeurotoxinasVenenos de aranhaCanais de cálcioCanal de cátion TRPA1PainAnalgesiaPhα1β peptideCTK 01512-2Voltage-activated calcium channelsTRPA1Analgesic effects of Phα1β toxin: a review of mechanisms of action involving pain pathwaysEfeitos analgésicos da toxina Phα1β: uma revisão de mecanismos de ação envolvendo as vias da dorinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://www.scielo.br/j/jvatitd/a/fsmrGLSSTVR7qvvwCRg9VFj/?lang=enJuliana Figueira da SilvaNancy Scardua BindaElizete Maria Rita PereiraMário Sérgio Lima de LavorLuciene Bruno VieiraAlessandra Hübner de SouzaFlávia Karine RigoHèlia Tenza FerrerCélio José de Castro JúniorJuliano FerreiraMarcus Vinicius Gomezapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/56258/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALAnalgesic effects of Phα1β toxin a review of mechanisms of action involving pain pathways.pdfAnalgesic effects of Phα1β toxin a review of mechanisms of action involving pain pathways.pdfapplication/pdf391627https://repositorio.ufmg.br/bitstream/1843/56258/2/Analgesic%20effects%20of%20Ph%ce%b11%ce%b2%20toxin%20a%20review%20of%20mechanisms%20of%20action%20involving%20pain%20pathways.pdf5f1772fbff1d1f2c2ecf300fba94b7fcMD521843/562582023-07-14 16:35:34.394oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-07-14T19:35:34Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.pt_BR.fl_str_mv |
Analgesic effects of Phα1β toxin: a review of mechanisms of action involving pain pathways |
dc.title.alternative.pt_BR.fl_str_mv |
Efeitos analgésicos da toxina Phα1β: uma revisão de mecanismos de ação envolvendo as vias da dor |
title |
Analgesic effects of Phα1β toxin: a review of mechanisms of action involving pain pathways |
spellingShingle |
Analgesic effects of Phα1β toxin: a review of mechanisms of action involving pain pathways Juliana Figueira da Silva Pain Analgesia Phα1β peptide CTK 01512-2 Voltage-activated calcium channels TRPA1 Dor Analgesia Analgésicos Neurotoxinas Venenos de aranha Canais de cálcio Canal de cátion TRPA1 |
title_short |
Analgesic effects of Phα1β toxin: a review of mechanisms of action involving pain pathways |
title_full |
Analgesic effects of Phα1β toxin: a review of mechanisms of action involving pain pathways |
title_fullStr |
Analgesic effects of Phα1β toxin: a review of mechanisms of action involving pain pathways |
title_full_unstemmed |
Analgesic effects of Phα1β toxin: a review of mechanisms of action involving pain pathways |
title_sort |
Analgesic effects of Phα1β toxin: a review of mechanisms of action involving pain pathways |
author |
Juliana Figueira da Silva |
author_facet |
Juliana Figueira da Silva Nancy Scardua Binda Elizete Maria Rita Pereira Mário Sérgio Lima de Lavor Luciene Bruno Vieira Alessandra Hübner de Souza Flávia Karine Rigo Hèlia Tenza Ferrer Célio José de Castro Júnior Juliano Ferreira Marcus Vinicius Gomez |
author_role |
author |
author2 |
Nancy Scardua Binda Elizete Maria Rita Pereira Mário Sérgio Lima de Lavor Luciene Bruno Vieira Alessandra Hübner de Souza Flávia Karine Rigo Hèlia Tenza Ferrer Célio José de Castro Júnior Juliano Ferreira Marcus Vinicius Gomez |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Juliana Figueira da Silva Nancy Scardua Binda Elizete Maria Rita Pereira Mário Sérgio Lima de Lavor Luciene Bruno Vieira Alessandra Hübner de Souza Flávia Karine Rigo Hèlia Tenza Ferrer Célio José de Castro Júnior Juliano Ferreira Marcus Vinicius Gomez |
dc.subject.por.fl_str_mv |
Pain Analgesia Phα1β peptide CTK 01512-2 Voltage-activated calcium channels TRPA1 |
topic |
Pain Analgesia Phα1β peptide CTK 01512-2 Voltage-activated calcium channels TRPA1 Dor Analgesia Analgésicos Neurotoxinas Venenos de aranha Canais de cálcio Canal de cátion TRPA1 |
dc.subject.other.pt_BR.fl_str_mv |
Dor Analgesia Analgésicos Neurotoxinas Venenos de aranha Canais de cálcio Canal de cátion TRPA1 |
description |
Phα1β is a neurotoxin purified from spider venom that acts as a high-voltage-activated (HVA) calcium channel blocker. This spider peptide has shown a high selectivity for N-type HVA calcium channels (NVACC) and an analgesic effect in several animal models of pain. Its activity was associated with a reduction in calcium transients, glutamate release, and reactive oxygen species production from the spinal cord tissue and dorsal ganglia root (DRG) in rats and mice. It has been reported that intrathecal (i.t.) administration of Phα1β to treat chronic pain reverted opioid tolerance with a safer profile than ω-conotoxin MVIIA, a highly selective NVACC blocker. Following a recent development of recombinant Phα1β (CTK 01512-2), a new molecular target, TRPA1, the structural arrangement of disulphide bridges, and an effect on glial plasticity have been identified. CTK 01512-2 reproduced the antinociceptive effects of the native toxin not only after the intrathecal but also after the intravenous administration. Herein, we review the Phα1β antinociceptive activity in the most relevant pain models and its mechanisms of action, highlighting the impact of CTK 01512-2 synthesis and its potential for multimodal analgesia. |
publishDate |
2021 |
dc.date.issued.fl_str_mv |
2021-11-22 |
dc.date.accessioned.fl_str_mv |
2023-07-14T19:35:34Z |
dc.date.available.fl_str_mv |
2023-07-14T19:35:34Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/56258 |
dc.identifier.doi.pt_BR.fl_str_mv |
https://doi.org/10.1590/1678-9199-JVATITD-2021-0001 |
dc.identifier.issn.pt_BR.fl_str_mv |
1678-9199 |
dc.identifier.orcid.pt_BR.fl_str_mv |
https://orcid.org/0000-0002-2906-517X https://orcid.org/0000-0003-0603-0342 https://orcid.org/0000-0003-0795-5320 https://orcid.org/0000-0002-3496-6749 https://orcid.org/0000-0002-6832-2765 https://orcid.org/0000-0002-9175-5761 https://orcid.org/0000-0002-0063-4471 https://orcid.org/0000-0002-9562-0602 https://orcid.org/0000-0002-6082-930X |
url |
https://doi.org/10.1590/1678-9199-JVATITD-2021-0001 http://hdl.handle.net/1843/56258 https://orcid.org/0000-0002-2906-517X https://orcid.org/0000-0003-0603-0342 https://orcid.org/0000-0003-0795-5320 https://orcid.org/0000-0002-3496-6749 https://orcid.org/0000-0002-6832-2765 https://orcid.org/0000-0002-9175-5761 https://orcid.org/0000-0002-0063-4471 https://orcid.org/0000-0002-9562-0602 https://orcid.org/0000-0002-6082-930X |
identifier_str_mv |
1678-9199 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Journal of Venomous Animals and Toxins including Tropical Diseases |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Universidade Federal de Minas Gerais |
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UFMG |
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Brasil |
dc.publisher.department.fl_str_mv |
ICB - DEPARTAMENTO DE FARMACOLOGIA |
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Universidade Federal de Minas Gerais |
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