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 language | English |
|---|---|
| Pages (from-to) | 556-563 |
| Number of pages | 8 |
| Journal | Neuropharmacology |
| Volume | 56 |
| DOIs | |
| State | Published - Feb 1 2009 |
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Keywords
- Allodynia
- CGX-1007
- Conus
- Neuropathic pain
- Spinal cord injury
- Ziconotide
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Pharmacology
Cite this
Antinociceptive effects of the marine snail peptides conantokin-G and conotoxin MVIIA alone and in combination in rat models of pain. / Hama, Aldric; Sagen, Jacqueline.
In: Neuropharmacology, Vol. 56, 01.02.2009, p. 556-563.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Antinociceptive effects of the marine snail peptides conantokin-G and conotoxin MVIIA alone and in combination in rat models of pain
AU - Hama, Aldric
AU - Sagen, Jacqueline
PY - 2009/2/1
Y1 - 2009/2/1
N2 - 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.
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.
KW - Allodynia
KW - CGX-1007
KW - Conus
KW - Neuropathic pain
KW - Spinal cord injury
KW - Ziconotide
UR - http://www.scopus.com/inward/record.url?scp=58549085757&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58549085757&partnerID=8YFLogxK
U2 - 10.1016/j.neuropharm.2008.10.008
DO - 10.1016/j.neuropharm.2008.10.008
M3 - Article
C2 - 19010337
AN - SCOPUS:58549085757
VL - 56
SP - 556
EP - 563
JO - Neuropharmacology
JF - Neuropharmacology
SN - 0028-3908
ER -