conotoxin-gv and Neuralgia

Cilnidipine is a dihydropyridine derivative that inhibits N-type and L-type voltage-gated Ca

Topics: Animals; Calcium Channel Blockers; Calcium Channels, L-Type; Calcium Channels, N-Type; Conotoxins; Dihydropyridines; Evoked Potentials; Long-Term Potentiation; Male; Mice; Nerve Fibers, Unmyelinated; Neuralgia; Nicardipine; Rats; Spinal Cord Dorsal Horn

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.

Topics: Analgesics; Animals; Conotoxins; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Hyperalgesia; Male; Motor Activity; Neuralgia; omega-Conotoxins; Pain Measurement; Pain Threshold; Rats; Rats, Sprague-Dawley; Reaction Time; Rotarod Performance Test; Time Factors