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 Oliveirabuc¹, Daniela Pereira Alves¹, Bruna Luiza Emerich¹, Suely Gomes de Figueiredo², Marta do Nascimento Cordeiro³, Márcia Helena Borges³, Michael Richardson³, Adriano Monteiro de Castro Pimenta¹, Igor Dimitri Gama Duarte⁴, Maria Elena de Lima^1  5

 

1 Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brasil.

2 Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espirito Santo (UFES), Vitória (ES), Brasil.

3 Centro de Pesquisa e Desenvolvimento Professor Carlos Diniz, Fundação Ezequiel Dias (FUNED), Belo Horizonte, MG, Brasil.

4 Departamento de Fisiologia e Farmacologia, Instituto de Ciências Biológicas (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brasil.

5 Instituto de Ensino e Pesquisa, Santa Casa de Belo Horizonte, Rua Domingos Vieira, 590, Santa Efigênia, Belo Horizonte, MG, CEP 30.150-240, Brasil.

 

ABSTRACT

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.

Conclusion:

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

 

Received: April 04, 2019.

Accepted: July 10, 2019.

 

Correspondence: mariaelena@santacasabh.org.br

 

Competing interests

The authors declare that they have no competing interests.

 

Authors' contributions

MEL proposed the project and, together with IDGD and DPA, supervised the research and revised the manuscript. MNC, MR, MHB and SGF isolated the toxin and performed its biochemical characterization. CFBO and DPA performed the nociceptive experiments and data analyses, besides writing the paper. BLE and AMCP reviewed the manuscript and participated in discussions during the work. All authors contributed extensively to the study presented in this article. Moreover, all authors read and approved the final manuscript.