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

43 Citations (Scopus)

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
Pages (from-to)556-563
Number of pages8
JournalNeuropharmacology
Volume56
DOIs
StatePublished - Feb 1 2009

Fingerprint

Conotoxins
Snails
Pain
Peptides
Spinal Cord Injuries
Spinal Injections
Pain Measurement
Ligation
Mollusk Venoms
Spinal Nerves
Spinal Cord Compression
Ion Channels
Formaldehyde
Analgesics
conotoxin GV
Wounds and Injuries

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

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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.",
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AB - 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.

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