Antinociceptive effects of the marine snail peptides conantokin-G and conotoxin MVIIA alone and in combination in rat models of pain

Aldric Hama, Jacqueline Sagen

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

There are a number of neurologically active ion channel blocking peptides derived from cone snail venom, such as conantokin-G and ω-conotoxin MVIIA. Conantokin-G inhibits NMDA receptors containing the NR2B subunit whereas ω-conotoxin MVIIA blocks N-type Ca2+ channels. Separately, these peptides induce antinociceptive effects in pre-clinical pain models following intrathecal injection. In the current study, the efficacies of these peptides were determined separately and in combination by intrathecal injection into rats with a spinal nerve ligation, in rats with a spinal cord compression injury and in the formalin test. Separately, both conantokin-G and ω-conotoxin MVIIA dose-dependently attenuated nociceptive responses in all of these models. However, at high antinociceptive doses for both formalin and nerve injury models, ω-conotoxin MVIIA evoked untoward side effects. Using isobolographic analysis, the combination of sub-antinociceptive doses of peptides demonstrated additive antinociception in rats with a nerve ligation and in the formalin test, without apparent adverse side effects. In a model of neuropathic spinal cord injury pain, which is clinically difficult to treat, the combination of conantokin-G and ω-conotoxin MVIIA resulted in robust synergistic antinociception. These data suggest that a combination of these peptides may be analgesic across diverse clinical pains with limited untoward side effects, and particularly potent for reducing spinal cord injury pain.

Original languageEnglish (US)
Pages (from-to)556-563
Number of pages8
JournalNeuropharmacology
Volume56
Issue number2
DOIs
StatePublished - Feb 2009

Keywords

  • Allodynia
  • CGX-1007
  • Conus
  • Neuropathic pain
  • Spinal cord injury
  • Ziconotide

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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