• Open Access

Spider peptide Phα1β induces analgesic effect in a model of cancer pain

Authors

  • Flavia Karine Rigo,

    1. Graduate Program in Biochemistry and Molecular Pharmacology, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil
    2. Graduate Program in Medicine and Biomedicine-Institute of Education and Research Santa Casa, Belo Horizonte, Minas Gerais, Brazil
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    • These authors contributed equally to this work.
  • Gabriela Trevisan,

    1. Graduate Program in Biological Sciences and Biochemistry Toxicology, Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil
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    • These authors contributed equally to this work.
  • Fernanda Rosa,

    1. Graduate Program in Biological Sciences and Biochemistry Toxicology, Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil
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  • Gerusa D. Dalmolin,

    1. Graduate Program in Biological Sciences and Biochemistry Toxicology, Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil
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  • Michel Fleith Otuki,

    1. Department of Pharmaceutical Sciences, State University of Parana, Ponta Grossa, Parana, Brazil
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  • Ana Paula Cueto,

    1. Graduate Program in Biological Sciences and Biochemistry Toxicology, Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil
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  • Célio José de Castro Junior,

    1. Graduate Program in Medicine and Biomedicine-Institute of Education and Research Santa Casa, Belo Horizonte, Minas Gerais, Brazil
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  • Marco Aurelio Romano-Silva,

    1. Graduate Program in Biochemistry and Molecular Pharmacology, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil
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  • Marta do N. Cordeiro,

    1. Ezequiel Dias Foundation, Belo Horizonte, Minas Gerais, Brazil
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  • Michael Richardson,

    1. Ezequiel Dias Foundation, Belo Horizonte, Minas Gerais, Brazil
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  • Juliano Ferreira,

    1. Graduate Program in Biological Sciences and Biochemistry Toxicology, Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil
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  • Marcus V. Gomez

    Corresponding author
    1. Graduate Program in Medicine and Biomedicine-Institute of Education and Research Santa Casa, Belo Horizonte, Minas Gerais, Brazil
    • Graduate Program in Biochemistry and Molecular Pharmacology, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil
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To whom correspondence should be addressed.

E-mail: marcusvgomez@gmail.com

Abstract

The marine snail peptide ziconotide (ω-conotoxin MVIIA) is used as an analgesic in cancer patients refractory to opioids, but may induce severe adverse effects. Animal venoms represent a rich source of novel drugs, so we investigated the analgesic effects and the side-effects of spider peptide Phα1β in a model of cancer pain in mice with or without tolerance to morphine analgesia. Cancer pain was induced by the inoculation of melanoma B16-F10 cells into the hind paw of C57BL/6 mice. After 14 days, painful hypersensitivity was detected and Phα1β or ω-conotoxin MVIIA (10–100 pmol/site) was intrathecally injected to evaluate the development of antinociception and side-effects in control and morphine-tolerant mice. The treatment with Phα1β or ω-conotoxin MVIIA fully reversed cancer-related painful hypersensitivity, with long-lasting results, at effective doses 50% of 48 (32–72) or 33 (21–53) pmol/site, respectively. Phα1β produced only mild adverse effects, whereas ω-conotoxin MVIIA induced dose-related side-effects in mice at analgesic doses (estimated toxic dose 50% of 30 pmol/site). In addition, we observed that Phα1β was capable of controlling cancer-related pain even in mice tolerant to morphine antinociception (100% of inhibition) and was able to partially restore morphine analgesia in such animals (56 ± 5% of inhibition). In this study, Phα1β was as efficacious as ω-conotoxin MVIIA in inducing analgesia in a model of cancer pain without producing severe adverse effects or losing efficacy in opioid-tolerant mice, indicating that Phα1β has a good profile for the treatment of cancer pain in patients.

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