Dados do Trabalho

Título

EFEITO ANTINOCICEPTIVO DA ADMNISTRAÇAO INTRAVENOSA DA FORMA RECOMBINANTE DO PEPTIDEO PHΑ1Β

Fundamentação/Introdução

Bloqueadores de canais para cálcio regulados por voltagem, quando injetados via intratecal (i.t.) tem ação analgésica em diversos modelos de dor animal. A Phα1β recombinante mostrou os mesmos efeitos analgésicos que a toxina nativa (derivada do veneno da aranha Phoneutria Nigriventer), quando injetada i.t.. Porém esta via de administração para drogas analgésicas limita o seu uso clinico em pacientes, sugerindo a busca por uma via parenteral menos invasiva

Objetivos

- Verificar o efeito antinociceptivo da administração do peptídeo recombinante da toxina Phα1β (Phα1βr) por via intravenosa (i.v.), em modelos de dor crônica (induzida por constrição crônica do nervo ciático CCI e paclitaxel PAC) e em um modelo de dor aguda induzida por PAC; Verificar os efeitos colaterais da administração do peptídeo Phα1βr i.v..

Delineamento e Métodos

No estudo experimental foram utilizados 72 ratos Wistar (12 grupos n=6) e 30 camundongos Balb-c (5 grupos n=6) machos. Afim de investigar o possível efeito antinociceptivo da administração do peptideo foram utilizados modelos de dor neuropática (induzida por CCI ou PAC) e dor aguda(induzida por PAC). Os ratos foram tratados com Phα1βr i.v. (0,006-0,6 mg/kg i.v.) ou PBS e avaliados através do teste de Von Frey.
Foram verificados também possíveis efeitos colaterais motores (através do teste de campo aberto), e bioquimicos (CKMB, TGO, TGP, LDH, lactato, creatinina e uréia) para as doses de 0,2-1,8 mg/kg, i.v. em camundongos.

O projeto foi aceito pelo comitê de ética (CEUA) da Universidade do Extremo Sul Catarinense.

Resultados

A Phα1βr (0,2mg/kg iv) reduziu amplamente a hipersensibilidade mecânica (nocicepção neuropática) induzida pela CCI. Os efeitos analgésicos duraram 4 horas, atingindo 67,7% ± 9,1% de inibição para a dose de 0,06 mg/kg (i.v.) e 100% de inibição (Imax = 100%) para a dose de 0,2 mg/kg (iv), com um ED50 de 0,02 (0,01-0,03) mg/kg.
A administração intravenosa de 0,2 mg/kg de Phα1βr inibiu a hiperalgesia mecânica na dor aguda e crônica até 4 horas após administração com 100% de inibição (Imax = 100%).
Não foram observadas mudanças significativas nas funções motoras e nos parâmetros bioquímicos para os efeitos colaterais avaliados. A Phα1βr não causou alterações no limiar mecânico dos grupos controle.

Conclusões/Considerações Finais

Os dados sugerem que a administração i.v da Phα1βr seja possível com antinocicepção induzida sem efeitos colaterais severos em roedores.

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Palavras-chave

Phα1β, admnistração intravenosa, antinocicepção, dor neuropática, lesão por constrição crônica, paclitaxel.

Área

Tema livre