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Antinociceptive effect of a novel armed spider peptide Tx3-5 in pathological pain models in mice.
Oliveira, Sara M; Silva, Cássia R; Trevisan, Gabriela; Villarinho, Jardel G; Cordeiro, Marta N; Richardson, Michael; Borges, Márcia H; Castro, Célio J; Gomez, Marcus V; Ferreira, Juliano.
Afiliación
  • Oliveira SM; Programa de Pós-graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil. saramarchesan@hotmail.com.
  • Silva CR; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Avenida Roraima 1000, Cidade Universitária, Santa Maria, RS, 97105-900, Brazil. saramarchesan@hotmail.com.
  • Trevisan G; Programa de Pós-graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
  • Villarinho JG; Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
  • Cordeiro MN; Programa de Pós-graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
  • Richardson M; Fundação Ezequiel Dias, Belo Horizonte, MG, Brazil.
  • Borges MH; Fundação Ezequiel Dias, Belo Horizonte, MG, Brazil.
  • Castro CJ; Fundação Ezequiel Dias, Belo Horizonte, MG, Brazil.
  • Gomez MV; Programa de Pós-graduação em Farmacologia Bioquímica e Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
  • Ferreira J; Nucleo de Pós-graduação, Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Belo Horizonte, MG, Brazil.
Pflugers Arch ; 468(5): 881-94, 2016 05.
Article en En | MEDLINE | ID: mdl-26898377
The venom of the Brazilian armed spider Phoneutria nigriventer is a rich source of biologically active peptides that have potential as analgesic drugs. In this study, we investigated the analgesic and adverse effects of peptide 3-5 (Tx3-5), purified from P. nigriventer venom, in several mouse models of pain. Tx3-5 was administered by intrathecal injection to mice selected as models of postoperative (plantar incision), neuropathic (partial sciatic nerve ligation) and cancer-related pain (inoculation with melanoma cells) in animals that were either sensitive or tolerant to morphine. Intrathecal administration of Tx3-5 (3-300 fmol/site) in mice could either prevent or reverse postoperative nociception, with a 50 % inhibitory dose (ID50) of 16.6 (3.2-87.2) fmol/site and a maximum inhibition of 87 ± 10 % at a dose of 30 fmol/site. Its effect was prevented by the selective activator of L-type calcium channel Bay-K8644 (10 µg/site). Tx3-5 (30 fmol/site) also produced a partial antinociceptive effect in a neuropathic pain model (inhibition of 67 ± 10 %). Additionally, treatment with Tx3-5 (30 fmol/site) nearly abolished cancer-related nociception with similar efficacy in both morphine-sensitive and morphine-tolerant mice (96 ± 7 and 100 % inhibition, respectively). Notably, Tx3-5 did not produce visible adverse effects at doses that produced antinociception and presented a TD50 of 1125 (893-1418) fmol/site. Finally, Tx3-5 did not alter the normal mechanical or thermal sensitivity of the animals or cause immunogenicity. Our results suggest that Tx3-5 is a strong drug candidate for the treatment of painful conditions.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Venenos de Araña / Neuropéptidos / Dolor en Cáncer / Analgésicos / Neuralgia / Neurotoxinas Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Pflugers Arch Año: 2016 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Venenos de Araña / Neuropéptidos / Dolor en Cáncer / Analgésicos / Neuralgia / Neurotoxinas Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Pflugers Arch Año: 2016 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Alemania