Analgesic and side effects of intravenous recombinant Pha1β
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | https://doi.org/10.1590/1678-9199-JVATITD-2019-0070 http://hdl.handle.net/1843/49139 |
Resumo: | Background: Intrathecal injection of voltage-sensitive calcium channel blocker peptide toxins exerts analgesic effect in several animal models of pain. Upon intrathecal administration, recombinant Phα1β exerts the same analgesic effects as the those of the native toxin. However, from a clinical perspective, the intrathecal administration limits the use of anesthetic drugs in patients. Therefore, this study aimed to investigate the possible antinociceptive effect of intravenous recombinant Phα1β in rat models of neuropathic pain, as well as its side effects on motor, cardiac (heart rate and blood pressure), and biochemical parameters. Methods: Male Wistar rats and male Balb-C mice were used in this study. Giotto Biotech® synthesized the recombinant version of Phα1β using Escherichia coli expression.In rats, neuropathic pain was induced by chronic constriction of the sciatic nerve and paclitaxel-induced acute and chronic ain. Mechanical sensitivity was evaluated using von Frey filaments. A radiotelemeter transmitter (TA11PA-C10; Data Sciences, St. Paul, MN, USA) was placed on the left carotid of mice for investigation of cardiovascular side effects. Locomotor activity data were evaluated using the open-field paradigm, and serum CKMB, TGO, TGP, LDH, lactate, creatinine, and urea levels were examined. Results: Intravenous administration of recombinant Phα1β toxin induced analgesia for up to 4 h, with ED50 of 0.02 (0.01-0.03) mg/kg, and reached the maximal effect (Emax = 100% antinociception) at a dose of 0.2 mg/kg. No significant changes were observed in any of the evaluated motor, cardiac or biochemical parameters. Conclusion: Our data suggest that intravenous administration of recombinant Phα1β may be feasible for drug-induced analgesia, without causing any severe side effects. |
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2023-01-25T15:59:21Z2023-01-25T15:59:21Z20202619https://doi.org/10.1590/1678-9199-JVATITD-2019-007016789199http://hdl.handle.net/1843/491390000-0002-6558-4639Background: Intrathecal injection of voltage-sensitive calcium channel blocker peptide toxins exerts analgesic effect in several animal models of pain. Upon intrathecal administration, recombinant Phα1β exerts the same analgesic effects as the those of the native toxin. However, from a clinical perspective, the intrathecal administration limits the use of anesthetic drugs in patients. Therefore, this study aimed to investigate the possible antinociceptive effect of intravenous recombinant Phα1β in rat models of neuropathic pain, as well as its side effects on motor, cardiac (heart rate and blood pressure), and biochemical parameters. Methods: Male Wistar rats and male Balb-C mice were used in this study. Giotto Biotech® synthesized the recombinant version of Phα1β using Escherichia coli expression.In rats, neuropathic pain was induced by chronic constriction of the sciatic nerve and paclitaxel-induced acute and chronic ain. Mechanical sensitivity was evaluated using von Frey filaments. A radiotelemeter transmitter (TA11PA-C10; Data Sciences, St. Paul, MN, USA) was placed on the left carotid of mice for investigation of cardiovascular side effects. Locomotor activity data were evaluated using the open-field paradigm, and serum CKMB, TGO, TGP, LDH, lactate, creatinine, and urea levels were examined. Results: Intravenous administration of recombinant Phα1β toxin induced analgesia for up to 4 h, with ED50 of 0.02 (0.01-0.03) mg/kg, and reached the maximal effect (Emax = 100% antinociception) at a dose of 0.2 mg/kg. No significant changes were observed in any of the evaluated motor, cardiac or biochemical parameters. Conclusion: Our data suggest that intravenous administration of recombinant Phα1β may be feasible for drug-induced analgesia, without causing any severe side effects.Introdução: A injeção intratecal de toxinas peptídicas bloqueadoras dos canais de cálcio sensíveis à voltagem exerce efeito analgésico em vários modelos animais de dor. Após administração intratecal, Phα1β recombinante exerce os mesmos efeitos analgésicos da toxina nativa. No entanto, do ponto de vista clínico, a administração intratecal limita o uso de drogas anestésicas em pacientes. Portanto, este estudo teve como objetivo investigar o possível efeito antinociceptivo do Phα1β recombinante intravenoso em modelos de dor neuropática em ratos, bem como seus efeitos colaterais nos parâmetros motores, cardíacos (frequência cardíaca e pressão arterial) e bioquímicos. Métodos: Ratos Wistar machos e camundongos Balb-C machos foram utilizados neste estudo. A Giotto Biotech® sintetizou a versão recombinante de Phα1β usando a expressão de Escherichia coli. Em ratos, a dor neuropática foi induzida por constrição crônica do nervo ciático e dor aguda e crônica induzida por paclitaxel. A sensibilidade mecânica foi avaliada usando filamentos de von Frey. Um transmissor de radiotelemetro (TA11PA-C10; Data Sciences, St. Paul, MN, EUA) foi colocado na carótida esquerda de camundongos para investigação de efeitos colaterais cardiovasculares. Os dados da atividade locomotora foram avaliados usando o paradigma de campo aberto, e os níveis séricos de CKMB, TGO, TGP, LDH, lactato, creatinina e uréia foram examinados. Resultados: A administração intravenosa de toxina Phα1β recombinante induziu analgesia por até 4 h, com ED50 de 0,02 (0,01-0,03) mg/kg, e atingiu o efeito máximo (Emax = 100% antinocicepção) na dose de 0,2 mg/kg. Não foram observadas alterações significativas em nenhum dos parâmetros motores, cardíacos ou bioquímicos avaliados. Conclusão: Nossos dados sugerem que a administração intravenosa de Phα1β recombinante pode ser viável para analgesia induzida por drogas, sem causar efeitos colaterais graves.porUniversidade Federal de Minas GeraisUFMGBrasilMED - DEPARTAMENTO DE SAÚDE MENTALJournal of venomous animals and toxins including tropical diseasesAnalgesiaNeuralgiaEfeitos Colaterais e Reações Adversas Relacionados a MedicamentosAtividade MotoraRecombinant Phα1βAnalgesiaNeuropathic painIntravenous drug delivery systemSide effectsCardiac functionMotor activityBiochemicalsAnalgesic and side effects of intravenous recombinant Pha1βAnalgésicos e efeitos colaterais de Pha1β recombinante intravenosoinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://www.scielo.br/j/jvatitd/a/mvYsWBBBDZDL8kfkXYm9PMk/?lang=enFlávia Karine RigoMarco Aurélio Romano SilvaCélio José de Castro JuniorThiago Mattar CunhaJuliano FerreiraMarcus Vínicius GomezMateus Fortes RossatoVanessa BorgesJuliana Figueira da SilvaElizete Maria Rita PereiraRicardo Andrez Machado de ÁvilaGabriela TrevisanDuana Carvalho Dos SantosDanuza Montijo Dinizapplication/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/1843/49139/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALAnalgesic and side effects of intravenous.pdfAnalgesic and side effects of intravenous.pdfapplication/pdf381768https://repositorio.ufmg.br/bitstream/1843/49139/2/Analgesic%20and%20side%20effects%20of%20intravenous.pdfef1a65e4a9335fb4958fa5a5f735160cMD521843/491392023-01-25 14:39:29.804oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-01-25T17:39:29Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.pt_BR.fl_str_mv |
Analgesic and side effects of intravenous recombinant Pha1β |
dc.title.alternative.pt_BR.fl_str_mv |
Analgésicos e efeitos colaterais de Pha1β recombinante intravenoso |
title |
Analgesic and side effects of intravenous recombinant Pha1β |
spellingShingle |
Analgesic and side effects of intravenous recombinant Pha1β Flávia Karine Rigo Recombinant Phα1β Analgesia Neuropathic pain Intravenous drug delivery system Side effects Cardiac function Motor activity Biochemicals Analgesia Neuralgia Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos Atividade Motora |
title_short |
Analgesic and side effects of intravenous recombinant Pha1β |
title_full |
Analgesic and side effects of intravenous recombinant Pha1β |
title_fullStr |
Analgesic and side effects of intravenous recombinant Pha1β |
title_full_unstemmed |
Analgesic and side effects of intravenous recombinant Pha1β |
title_sort |
Analgesic and side effects of intravenous recombinant Pha1β |
author |
Flávia Karine Rigo |
author_facet |
Flávia Karine Rigo Marco Aurélio Romano Silva Célio José de Castro Junior Thiago Mattar Cunha Juliano Ferreira Marcus Vínicius Gomez Mateus Fortes Rossato Vanessa Borges Juliana Figueira da Silva Elizete Maria Rita Pereira Ricardo Andrez Machado de Ávila Gabriela Trevisan Duana Carvalho Dos Santos Danuza Montijo Diniz |
author_role |
author |
author2 |
Marco Aurélio Romano Silva Célio José de Castro Junior Thiago Mattar Cunha Juliano Ferreira Marcus Vínicius Gomez Mateus Fortes Rossato Vanessa Borges Juliana Figueira da Silva Elizete Maria Rita Pereira Ricardo Andrez Machado de Ávila Gabriela Trevisan Duana Carvalho Dos Santos Danuza Montijo Diniz |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Flávia Karine Rigo Marco Aurélio Romano Silva Célio José de Castro Junior Thiago Mattar Cunha Juliano Ferreira Marcus Vínicius Gomez Mateus Fortes Rossato Vanessa Borges Juliana Figueira da Silva Elizete Maria Rita Pereira Ricardo Andrez Machado de Ávila Gabriela Trevisan Duana Carvalho Dos Santos Danuza Montijo Diniz |
dc.subject.por.fl_str_mv |
Recombinant Phα1β Analgesia Neuropathic pain Intravenous drug delivery system Side effects Cardiac function Motor activity Biochemicals |
topic |
Recombinant Phα1β Analgesia Neuropathic pain Intravenous drug delivery system Side effects Cardiac function Motor activity Biochemicals Analgesia Neuralgia Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos Atividade Motora |
dc.subject.other.pt_BR.fl_str_mv |
Analgesia Neuralgia Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos Atividade Motora |
description |
Background: Intrathecal injection of voltage-sensitive calcium channel blocker peptide toxins exerts analgesic effect in several animal models of pain. Upon intrathecal administration, recombinant Phα1β exerts the same analgesic effects as the those of the native toxin. However, from a clinical perspective, the intrathecal administration limits the use of anesthetic drugs in patients. Therefore, this study aimed to investigate the possible antinociceptive effect of intravenous recombinant Phα1β in rat models of neuropathic pain, as well as its side effects on motor, cardiac (heart rate and blood pressure), and biochemical parameters. Methods: Male Wistar rats and male Balb-C mice were used in this study. Giotto Biotech® synthesized the recombinant version of Phα1β using Escherichia coli expression.In rats, neuropathic pain was induced by chronic constriction of the sciatic nerve and paclitaxel-induced acute and chronic ain. Mechanical sensitivity was evaluated using von Frey filaments. A radiotelemeter transmitter (TA11PA-C10; Data Sciences, St. Paul, MN, USA) was placed on the left carotid of mice for investigation of cardiovascular side effects. Locomotor activity data were evaluated using the open-field paradigm, and serum CKMB, TGO, TGP, LDH, lactate, creatinine, and urea levels were examined. Results: Intravenous administration of recombinant Phα1β toxin induced analgesia for up to 4 h, with ED50 of 0.02 (0.01-0.03) mg/kg, and reached the maximal effect (Emax = 100% antinociception) at a dose of 0.2 mg/kg. No significant changes were observed in any of the evaluated motor, cardiac or biochemical parameters. Conclusion: Our data suggest that intravenous administration of recombinant Phα1β may be feasible for drug-induced analgesia, without causing any severe side effects. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020 |
dc.date.accessioned.fl_str_mv |
2023-01-25T15:59:21Z |
dc.date.available.fl_str_mv |
2023-01-25T15:59:21Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/49139 |
dc.identifier.doi.pt_BR.fl_str_mv |
https://doi.org/10.1590/1678-9199-JVATITD-2019-0070 |
dc.identifier.issn.pt_BR.fl_str_mv |
16789199 |
dc.identifier.orcid.pt_BR.fl_str_mv |
0000-0002-6558-4639 |
url |
https://doi.org/10.1590/1678-9199-JVATITD-2019-0070 http://hdl.handle.net/1843/49139 |
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16789199 0000-0002-6558-4639 |
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por |
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por |
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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 |
dc.publisher.initials.fl_str_mv |
UFMG |
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Brasil |
dc.publisher.department.fl_str_mv |
MED - DEPARTAMENTO DE SAÚDE MENTAL |
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Universidade Federal de Minas Gerais |
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