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January 1, 2011Molecular PainOpen Access

mGlu2 Metabotropic Glutamate Receptors Restrain Inflammatory Pain and Mediate the Analgesic Activity of Dual mGlu2/mGlu3 Receptor Agonists

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Authors

MZMagda ZammataroSCSantina ChiechioMMMichael C. Montana

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Overview

Preclinical knockout study reveals mGlu2 mediates dual mGlu2/mGlu3 agonist analgesia in mice, highlighting subtype-specific pain control targets.

Key Points

  • To determine the individual contributions of mGlu2 and mGlu3 receptor subtypes to endogenous inflammatory pain suppression and to the pain-relieving effects of mixed mGlu2/3 receptor agonists.
  • Assessed pain responses in mGlu2-deficient (mGlu2-/-) and mGlu3-deficient (mGlu3-/-) mice compared to wild-type littermates using the biphasic formalin test.
  • Administered the dual mGlu2/3 agonist LY379268 (3 mg/kg, intraperitoneally) as a single dose or repeated for 5 consecutive days to evaluate acute analgesia and analgesic tolerance.
  • mGlu2-/- mice exhibited a significantly increased pain response during the second phase of the formalin test relative to wild-type mice, whereas mGlu3-/- mice showed no significant pain sensitivity differences in either phase.
  • Single-dose LY379268 significantly reduced pain behaviors in both phases in wild-type and mGlu3-/- mice, but produced no analgesic effect in mGlu2-/- mice.
  • Tolerance to the analgesic effects of LY379268 developed after 5 consecutive days of treatment in mGlu3-/- mice.

Cite This Study

Zammataro et al. (2011) studied this question.

synapsesocial.com/papers/6a96d253132cd8a75e579dd1https://doi.org/10.1186/1744-8069-7-6
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