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Métodos Terapêuticos e Terapias MTCI
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1.
Neuropharmacology ; 71: 237-46, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23597507

RESUMO

Phα1ß toxin is a peptide purified from the venom of the armed spider Phoneutria nigriventer, with markedly antinociceptive action in models of acute and persistent pain in rats. Similarly to ziconotide, its analgesic action is related to inhibition of high voltage activated calcium channels with more selectivity for N-type. In this study we evaluated the effect of Phα1ß when injected peripherally or intrathecally in a rat model of spontaneous pain induced by capsaicin. We also investigated the effect of Phα1ß on Ca²âº transients in cultured dorsal root ganglia (DRG) neurons and HEK293 cells expressing the TRPV1 receptor. Intraplantar or intrathecal administered Phα1ß reduced both nocifensive behavior and mechanical hypersensitivity induced by capsaicin similarly to that observed with SB366791, a specific TRPV1 antagonist. Peripheral nifedipine and mibefradil did also decrease nociceptive behavior induced by intraplantar capsaicin. In contrast, ω-conotoxin MVIIA (a selective N-type Ca²âº channel blocker) was effective only when administered intrathecally. Phα1ß, MVIIA and SB366791 inhibited, with similar potency, the capsaicin-induced Ca²âº transients in DRG neurons. The simultaneous administration of Phα1ß and SB366791 inhibited the capsaicin-induced Ca²âº transients that were additive suggesting that they act through different targets. Moreover, Phα1ß did not inhibit capsaicin-activated currents in patch-clamp recordings of HEK293 cells that expressed TRPV1 receptors. Our results show that Phα1ß may be effective as a therapeutic strategy for pain and this effect is not related to the inhibition of TRPV1 receptors.


Assuntos
Analgésicos não Narcóticos/uso terapêutico , Modelos Animais de Doenças , Gânglios Espinais/efeitos dos fármacos , Moduladores de Transporte de Membrana/uso terapêutico , Neuralgia/tratamento farmacológico , Neurônios/efeitos dos fármacos , Venenos de Aranha/uso terapêutico , Analgésicos não Narcóticos/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Capsaicina , Células Cultivadas , Gânglios Espinais/citologia , Gânglios Espinais/metabolismo , Gânglios Espinais/patologia , Células HEK293 , Humanos , Proteínas de Insetos/farmacologia , Proteínas de Insetos/uso terapêutico , Masculino , Moduladores de Transporte de Membrana/farmacologia , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neuralgia/metabolismo , Neuralgia/patologia , Neurônios/citologia , Neurônios/metabolismo , Neurônios/patologia , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Ratos , Ratos Wistar , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Venenos de Aranha/farmacologia , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo
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