δ-Ctenitoxin-Pn1a, a Peptide from Phoneutria nigriventer Spider Venom, Shows Antinociceptive Effect Involving Opioid and Cannabinoid Systems, in Rats

PnTx4(6-1), henceforth renamed δ-Ctenitoxin-Pn1a (δ-CNTX-Pn1a), a peptide from Phoneutria nigriventer spider venom, initially described as an insect toxin, binds to site 3 of sodium channels in nerve cord synaptosomes and slows down sodium current inactivation in isolated axons in cockroaches (Perip...

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Main Authors: Bruna Luiza Emerich, Renata C. M. Ferreira, Marta N. Cordeiro, Márcia Helena Borges, Adriano M. C. Pimenta, Suely G. Figueiredo, Igor Dimitri G. Duarte, Maria Elena de Lima
Format: Article
Language:English
Published: MDPI AG 2016-04-01
Series:Toxins
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Online Access:http://www.mdpi.com/2072-6651/8/4/106
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author Bruna Luiza Emerich
Renata C. M. Ferreira
Marta N. Cordeiro
Márcia Helena Borges
Adriano M. C. Pimenta
Suely G. Figueiredo
Igor Dimitri G. Duarte
Maria Elena de Lima
author_facet Bruna Luiza Emerich
Renata C. M. Ferreira
Marta N. Cordeiro
Márcia Helena Borges
Adriano M. C. Pimenta
Suely G. Figueiredo
Igor Dimitri G. Duarte
Maria Elena de Lima
author_sort Bruna Luiza Emerich
collection DOAJ
description PnTx4(6-1), henceforth renamed δ-Ctenitoxin-Pn1a (δ-CNTX-Pn1a), a peptide from Phoneutria nigriventer spider venom, initially described as an insect toxin, binds to site 3 of sodium channels in nerve cord synaptosomes and slows down sodium current inactivation in isolated axons in cockroaches (Periplaneta americana). δ-CNTX-Pn1a does not cause any apparent toxicity to mice, when intracerebroventricularly injected (30 μg). In this study, we evaluated the antinociceptive effect of δ-CNTX-Pn1a in three animal pain models and investigated its mechanism of action in acute pain. In the inflammatory pain model, induced by carrageenan, δ-CNTX-Pn1a restored the nociceptive threshold of rats, when intraplantarly injected, 2 h and 30 min after carrageenan administration. Concerning the neuropathic pain model, δ-CNTX-Pn1a, when intrathecally administered, reversed the hyperalgesia evoked by sciatic nerve constriction. In the acute pain model, induced by prostaglandin E2, intrathecal administration of δ-CNTX-Pn1a caused a dose-dependent antinociceptive effect. Using antagonists of the receptors, we showed that the antinociceptive effect of δ-CNTX-Pn1a involves both the cannabinoid system, through CB1 receptors, and the opioid system, through μ and δ receptors. Our data show, for the first time, that δ-Ctenitoxin-Pn1a is able to induce antinociception in inflammatory, neuropathic and acute pain models.
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spelling doaj.art-eed7a3072e8b48cb8b331e9fe1a3a28d2022-12-22T02:18:49ZengMDPI AGToxins2072-66512016-04-018410610.3390/toxins8040106toxins8040106δ-Ctenitoxin-Pn1a, a Peptide from Phoneutria nigriventer Spider Venom, Shows Antinociceptive Effect Involving Opioid and Cannabinoid Systems, in RatsBruna Luiza Emerich0Renata C. M. Ferreira1Marta N. Cordeiro2Márcia Helena Borges3Adriano M. C. Pimenta4Suely G. Figueiredo5Igor Dimitri G. Duarte6Maria Elena de Lima7Departmento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte, MG 31270-901, BrazilDepartmento de Farmacologia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte, MG 31270-901, BrazilFundação Ezequiel Dias, Rua Conde Pereira Carneiro, 80, Belo Horizonte, MG 30510010, BrazilFundação Ezequiel Dias, Rua Conde Pereira Carneiro, 80, Belo Horizonte, MG 30510010, BrazilDepartmento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte, MG 31270-901, BrazilDepartamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Av. Marechal Campos, 1468, Vitória, ES 29040-900, BrazilDepartmento de Farmacologia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte, MG 31270-901, BrazilDepartmento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte, MG 31270-901, BrazilPnTx4(6-1), henceforth renamed δ-Ctenitoxin-Pn1a (δ-CNTX-Pn1a), a peptide from Phoneutria nigriventer spider venom, initially described as an insect toxin, binds to site 3 of sodium channels in nerve cord synaptosomes and slows down sodium current inactivation in isolated axons in cockroaches (Periplaneta americana). δ-CNTX-Pn1a does not cause any apparent toxicity to mice, when intracerebroventricularly injected (30 μg). In this study, we evaluated the antinociceptive effect of δ-CNTX-Pn1a in three animal pain models and investigated its mechanism of action in acute pain. In the inflammatory pain model, induced by carrageenan, δ-CNTX-Pn1a restored the nociceptive threshold of rats, when intraplantarly injected, 2 h and 30 min after carrageenan administration. Concerning the neuropathic pain model, δ-CNTX-Pn1a, when intrathecally administered, reversed the hyperalgesia evoked by sciatic nerve constriction. In the acute pain model, induced by prostaglandin E2, intrathecal administration of δ-CNTX-Pn1a caused a dose-dependent antinociceptive effect. Using antagonists of the receptors, we showed that the antinociceptive effect of δ-CNTX-Pn1a involves both the cannabinoid system, through CB1 receptors, and the opioid system, through μ and δ receptors. Our data show, for the first time, that δ-Ctenitoxin-Pn1a is able to induce antinociception in inflammatory, neuropathic and acute pain models.http://www.mdpi.com/2072-6651/8/4/106spider toxinδ-Ctenitoxin-Pn1aPnTx4(6-1)Phoneutria nigriventerspider venomantinociception
spellingShingle Bruna Luiza Emerich
Renata C. M. Ferreira
Marta N. Cordeiro
Márcia Helena Borges
Adriano M. C. Pimenta
Suely G. Figueiredo
Igor Dimitri G. Duarte
Maria Elena de Lima
δ-Ctenitoxin-Pn1a, a Peptide from Phoneutria nigriventer Spider Venom, Shows Antinociceptive Effect Involving Opioid and Cannabinoid Systems, in Rats
Toxins
spider toxin
δ-Ctenitoxin-Pn1a
PnTx4(6-1)
Phoneutria nigriventer
spider venom
antinociception
title δ-Ctenitoxin-Pn1a, a Peptide from Phoneutria nigriventer Spider Venom, Shows Antinociceptive Effect Involving Opioid and Cannabinoid Systems, in Rats
title_full δ-Ctenitoxin-Pn1a, a Peptide from Phoneutria nigriventer Spider Venom, Shows Antinociceptive Effect Involving Opioid and Cannabinoid Systems, in Rats
title_fullStr δ-Ctenitoxin-Pn1a, a Peptide from Phoneutria nigriventer Spider Venom, Shows Antinociceptive Effect Involving Opioid and Cannabinoid Systems, in Rats
title_full_unstemmed δ-Ctenitoxin-Pn1a, a Peptide from Phoneutria nigriventer Spider Venom, Shows Antinociceptive Effect Involving Opioid and Cannabinoid Systems, in Rats
title_short δ-Ctenitoxin-Pn1a, a Peptide from Phoneutria nigriventer Spider Venom, Shows Antinociceptive Effect Involving Opioid and Cannabinoid Systems, in Rats
title_sort δ ctenitoxin pn1a a peptide from phoneutria nigriventer spider venom shows antinociceptive effect involving opioid and cannabinoid systems in rats
topic spider toxin
δ-Ctenitoxin-Pn1a
PnTx4(6-1)
Phoneutria nigriventer
spider venom
antinociception
url http://www.mdpi.com/2072-6651/8/4/106
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