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Antinociceptive effects of the marine snail peptides conantokin-G and conotoxin MVIIA alone and in combination in rat models of pain.
Neuropharmacology. 2009 Feb; 56(2):556-63.N

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+Show Affiliations

The Miami Project to Cure Paralysis, University of Miami, Miller School of Medicine, 1095 NW 14th Terrace, R-48, Miami, FL 33136, USA. ahama@med.miami.eduNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19010337

Citation

Hama, Aldric, and Jacqueline Sagen. "Antinociceptive Effects of the Marine Snail Peptides conantokin-G and Conotoxin MVIIA Alone and in Combination in Rat Models of Pain." Neuropharmacology, vol. 56, no. 2, 2009, pp. 556-63.
Hama A, Sagen J. Antinociceptive effects of the marine snail peptides conantokin-G and conotoxin MVIIA alone and in combination in rat models of pain. Neuropharmacology. 2009;56(2):556-63.
Hama, A., & Sagen, J. (2009). Antinociceptive effects of the marine snail peptides conantokin-G and conotoxin MVIIA alone and in combination in rat models of pain. Neuropharmacology, 56(2), 556-63. https://doi.org/10.1016/j.neuropharm.2008.10.008
Hama A, Sagen J. Antinociceptive Effects of the Marine Snail Peptides conantokin-G and Conotoxin MVIIA Alone and in Combination in Rat Models of Pain. Neuropharmacology. 2009;56(2):556-63. PubMed PMID: 19010337.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2008/10/26/ PY - 2008/08/29/received PY - 2008/10/18/revised PY - 2008/10/21/accepted PY - 2008/11/18/pubmed PY - 2009/7/2/medline PY - 2008/11/18/entrez SP - 556 EP - 63 JF - Neuropharmacology JO - Neuropharmacology VL - 56 IS - 2 N2 - 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. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/19010337/Antinociceptive_effects_of_the_marine_snail_peptides_conantokin_G_and_conotoxin_MVIIA_alone_and_in_combination_in_rat_models_of_pain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(08)00499-1 DB - PRIME DP - Unbound Medicine ER -