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

Abstract

There are a number of neurologically active ion channel blocking peptides derived from cone snail venom, such as conantokin-G and omega-conotoxin MVIIA. Conantokin-G inhibits NMDA receptors containing the NR2B subunit whereas omega-conotoxin MVIIA blocks N-type Ca(2+) 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 omega-conotoxin MVIIA dose-dependently attenuated nociceptive responses in all of these models. However, at high antinociceptive doses for both formalin and nerve injury models, omega-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 omega-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.

• Authors: Aldric Hama, Jacqueline Sagen
• Journal: Neuropharmacology (Neuropharmacology) Vol. 56 Issue 2 Pg. 556-63 (Feb 2009) ISSN: 0028-3908 [Print] England
• PMID: 19010337 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Conotoxins
• omega-Conotoxins
• ziconotide
• conotoxin GV

Topics

• Analgesics (therapeutic use)
• Animals
• Conotoxins (therapeutic use)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Synergism
• Hyperalgesia (drug therapy)
• Male
• Motor Activity (drug effects)
• Neuralgia (drug therapy)
• Pain Measurement
• Pain Threshold (drug effects)
• Rats
• Rats, Sprague-Dawley
• Reaction Time (drug effects)
• Rotarod Performance Test
• Time Factors
• omega-Conotoxins (therapeutic use)