title: δ-Ctenitoxin-Pn1a, a Peptide from Phoneutria nigriventer Spider Venom, Shows Antinociceptive Effect Involving Opioid and Cannabinoid Systems, in Rats.
abstract: 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.
authors.affiliation: Departmento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte, MG 31270-901, Brazil. brunaemerich@gmail.com.
authors.forename: Bruna Luiza
authors.initials: BL
authors.lastname: Emerich
authors.affiliation: Departmento de Farmacologia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte, MG 31270-901, Brazil. recmferreira@gmail.com.
authors.forename: Renata C M
authors.initials: RC
authors.lastname: Ferreira
authors.affiliation: Fundação Ezequiel Dias, Rua Conde Pereira Carneiro, 80, Belo Horizonte, MG 30510010, Brazil. martadonascimento.phoneutria@gmail.com.
authors.forename: Marta N
authors.initials: MN
authors.lastname: Cordeiro
authors.affiliation: Fundação Ezequiel Dias, Rua Conde Pereira Carneiro, 80, Belo Horizonte, MG 30510010, Brazil. mhborgesb@gmail.com.
authors.forename: Márcia Helena
authors.initials: MH
authors.lastname: Borges
authors.affiliation: Departmento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte, MG 31270-901, Brazil. apimenta@icb.ufmg.br.
authors.forename: Adriano M C
authors.initials: AM
authors.lastname: Pimenta
authors.affiliation: Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Av. Marechal Campos, 1468, Vitória, ES 29040-900, Brazil. suelygf@gmail.com.
authors.forename: Suely G
authors.initials: SG
authors.lastname: Figueiredo
authors.affiliation: Departmento de Farmacologia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte, MG 31270-901, Brazil. dimitri@icb.ufmg.br.
authors.forename: Igor Dimitri G
authors.initials: ID
authors.lastname: Duarte
authors.affiliation: Departmento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte, MG 31270-901, Brazil. melenalima@icb.ufmg.br.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: de Lima
mesh_terms: D059787:Acute Pain / Q000188:drug therapy* / Q000378:metabolism; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D060829:Arthropod Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D002351:Carrageenan; D015232:Dinoprostone; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D009437:Neuralgia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism; D012584:Sciatic Nerve / Q000293:injuries; D013111:Spider Venoms / Q000737:chemistry; D013112:Spiders
chemical_list: D000700:Analgesics; D060829:Arthropod Proteins; D063387:Cannabinoid Receptor Antagonists; D009292:Narcotic Antagonists; D010455:Peptides; D043882:Receptors, Cannabinoid; D011957:Receptors, Opioid; D013111:Spider Venoms; D002351:Carrageenan; D015232:Dinoprostone
keywords: Phoneutria nigriventer; PnTx4(6-1); antinociception; spider toxin; spider venom; δ-Ctenitoxin-Pn1a