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An Evaluation of the Antinociceptive Effects of Phα1β, a Neurotoxin from the Spider Phoneutria nigriventer, and ω-Conotoxin MVIIA, a Cone Snail Conus magus Toxin, in Rat Model of Inflammatory and Neuropathic Pain

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Abstract

Voltage-sensitive calcium channels (VSCCs) underlie cell excitability and are involved in the mechanisms that generate and maintain neuropathic and inflammatory pain. We evaluated in rats the effects of two VSCC blockers, ω-conotoxin MVIIA and Phα1β, in models of inflammatory and neuropathic pain induced with complete Freund’s adjuvant (CFA) and chronic constrictive injury (CCI), respectively. We also evaluated the effects of the toxins on capsaicin-induced Ca2+ influx in dorsal root ganglion (DRG) neurons obtained from rats exposed to both models of pain. A single intrathecal injection of Phα1β reversibly inhibits CFA and CCI-induced mechanical hyperalgesia longer than a single injection of ω-conotoxin MVIIA. Phα1β and MVIIA also inhibited capsaicin-induced Ca2+ influx in DRG neurons. The inhibitory effect of Phα1β on capsaicin-induced calcium transients in DRG neurons was greater in the CFA model of pain, while the inhibitory effect of ω-conotoxin MVIIA was greater in the CCI model. The management of chronic inflammatory and neuropathic pain is still a major challenge for clinicians. Phα1β, a reversible inhibitor of VSCCs with a preference for N-type Ca2+ channels, has potential as a novel therapeutic agent for inflammatory and neuropathic pain. Clinical studies are necessary to establish the role of Phα1β in the treatment of chronic pain.

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Acknowledgments

Supported by INCT Medicina Molecular, MCT/CNPq, Capes, Pronex and Fapemig. The authors A. H. S., J. F., M. N. C., L. B. V., M. R., R. S. G., and M. V. G. declare they have deposited a patent covering the use of Phα1β for pain management. A. H. S. and C. J. C. are post doctors fellows from Capes.

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Authors and Affiliations

  1. Programa de Pós-Graduação em Medicina Molecular, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

    Alessandra Hubner de Souza, Célio J. Castro Jr., Flavia Karine Rigo, Renato Santiago Gomez & Marco Aurélio Romano Silva

  2. Programa de Pós-Graduação em Biomedicina, Santa Casa de Belo Horizonte, Belo Horizonte, Brazil

    Célio J. Castro Jr., Danuza Montijo Diniz & Marcus Vinicius Gomez

  3. Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil

    Sara Marchesan de Oliveira & Juliano Ferreira

  4. Fundação Ezequiel Dias, Belo Horizonte, MG, Brazil

    Marcia Helena Borges & Marta Nascimento Cordeiro

  5. Laboratório de Neurociência, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 190, Sala 114, Belo Horizonte, MG, 31340-300, Brazil

    Marco Aurélio Romano Silva & Marcus Vinicius Gomez

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  1. Alessandra Hubner de Souza
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  2. Célio J. Castro Jr.
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  3. Flavia Karine Rigo
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  11. Marcus Vinicius Gomez
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Correspondence to Marcus Vinicius Gomez.

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de Souza, A.H., Castro, C.J., Rigo, F.K. et al. An Evaluation of the Antinociceptive Effects of Phα1β, a Neurotoxin from the Spider Phoneutria nigriventer, and ω-Conotoxin MVIIA, a Cone Snail Conus magus Toxin, in Rat Model of Inflammatory and Neuropathic Pain. Cell Mol Neurobiol 33, 59–67 (2013). https://doi.org/10.1007/s10571-012-9871-x

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  • DOI: https://doi.org/10.1007/s10571-012-9871-x

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