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Antinociceptive effect of PnTx4(5-5), a peptide from Phoneutria nigriventer spider venom, in rat models and the involvement of glutamatergic system

Camila Franco Batista Oliveira, Daniela Pereira Alves, Bruna Luiza Emerich, Suely Gomes de Figueiredo, Marta do Nascimento Cordeiro, Márcia Helena Borges, Michael Richardson, Adriano Monteiro de Castro Pimenta, Igor Dimitri Gama Duarte and Maria Elena de Lima

J Venom Anim Toxins incl Trop Dis, 2019, 25:e20190022
Received: 04 April 2019 | Accepted: 10 July 2019 | Published online: 12 August 2019


Background: The venom of Phoneutria nigriventer spider is a source of numerous bioactive substances, including some toxins active in insects. An example is PnTx4(5-5) that shows a high insecticidal activity and no apparent toxicity to mice, although it inhibited NMDA-evoked currents in rat hippocampal neurons. In this work the analgesic activity of PnTx4(5-5) (renamed Γ-ctenitoxin-Pn1a) was investigated. Methods: The antinociceptive activity was evaluated using the paw pressure test in rats, after hyperalgesia induction with intraplantar injection of carrageenan or prostaglandin E2 (PGE2). Results: PnTx4(5-5), subcutaneously injected, was able to reduce the hyperalgesia induced by PGE2 in rat paw, demonstrating a systemic effect. PnTx4(5-5) administered in the plantar surface of the paw caused a peripheral and dose-dependent antinociceptive effect on hyperalgesia induced by carrageenan or PGE2. The hyperalgesic effect observed in these two pain models was completely reversed with 5 µg of PnTx4(5-5). Intraplantar administration of L-glutamate induced hyperalgesic effect that was significantly reverted by 5 μg of PnTx4(5-5) injection in rat paw. Conclusions: The antinociceptive effect for PnTx4(5-5) was demonstrated against different rat pain models, i.e. induced by PGE2, carrageenan or glutamate. We suggest that the antinociceptive effect of PnTx4(5-5) may be related to an inhibitory activity on the glutamatergic system.


Keywords​: Spider toxin, Γ-ctenitoxin-Pn1a; PnTx4(5-5), Phoneutria nigriventer, Antinociception, Glutamate.

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