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Molecular Pain
Published in: Molecular Pain 1/2011

Open Access 01-12-2011 | Short report

mGlu2 metabotropic glutamate receptors restrain inflammatory pain and mediate the analgesic activity of dual mGlu2/mGlu3 receptor agonists

Authors: Magda Zammataro, Santina Chiechio, Michael C Montana, Anna Traficante, Agata Copani, Ferdinando Nicoletti, Robert W Gereau IV

Published in: Molecular Pain | Issue 1/2011

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Abstract

Group II metabotropic glutamate receptors (mGluRs) couple to the inhibitory G-protein Gi. The group II mGluRs include two subtypes, mGlu2 and mGlu3, and their pharmacological activation produces analgesic effects in inflammatory and neuropathic pain states. However, the specific contribution of each one of the two subtypes has not been clarified due to the lack of selective orthosteric ligands that can discriminate between mGlu2 and mGlu3 subtypes.
In this study we used mGlu2 or mGlu3 knock-out mice to dissect the specific role for these two receptors in the endogenous control of inflammatory pain and their specific contribution to the analgesic activity of mixed mGlu2/3 receptor agonists.
Our results showed that mGlu2-/- mice display a significantly greater pain response compared to their wild type littermates. Interestingly the increased pain sensitivity in mGlu2-/- mice occurred only in the second phase of the formalin test. No differences were observed in the first phase. In contrast, mGlu3-/- mice did not significantly differ from their wild type littermates in either phase of the formalin test.
When systemically injected, a single administration of the mGlu2/3 agonist, LY379268 (3 mg/kg, ip), showed a significant reduction of both phases in wild-type mice and in mGlu3-/- but not in mGlu2-/- mice. However tolerance to the analgesic effect of LY379268 (3 mg/kg, ip) in mGlu3-/- mice developed following 5 consecutive days of injection.
Taken together, these results demonstrate that: (i) mGlu2 receptors play a predominant role over mGlu3 receptors in the control of inflammatory pain in mice; (ii) the analgesic activity of mixed mGlu2/3 agonists is entirely mediated by the activation of the mGlu2 subtype and (iii) the development of tolerance to the analgesic effect of mGlu2/3 agonists develops despite the lack of mGlu3 receptors.
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Metadata
Title
mGlu2 metabotropic glutamate receptors restrain inflammatory pain and mediate the analgesic activity of dual mGlu2/mGlu3 receptor agonists
Authors
Magda Zammataro
Santina Chiechio
Michael C Montana
Anna Traficante
Agata Copani
Ferdinando Nicoletti
Robert W Gereau IV
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Molecular Pain / Issue 1/2011
Electronic ISSN: 1744-8069
DOI
https://doi.org/10.1186/1744-8069-7-6

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