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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

Group I Metabotropic Glutamate Receptor Antagonists Block Secondary Thermal Hyperalgesia in Rats with Knee Joint Inflammation

Liping Zhang, Ying Lu, Ying Chen and Karin N. Westlund
Journal of Pharmacology and Experimental Therapeutics January 2002, 300 (1) 149-156; DOI: https://doi.org/10.1124/jpet.300.1.149
Liping Zhang
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Ying Lu
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Ying Chen
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Karin N. Westlund
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Abstract

Activation of ionotropic glutamate receptors has been shown previously to be essential for the development of secondary thermal hyperalgesia. The present study assessed involvement of group I metabotropic glutamate receptors (mGlu) in both the induction and maintenance phases of secondary thermal hyperalgesia initiated by knee joint inflammation in rats. The dose dependence of each drug in antagonism of thermal hypersensitivity was demonstrated in pre- and post-treatment paradigms. Knee joint inflammation was induced by injection of kaolin and carrageenan. Four hours later the paw withdrawal latencies were significantly shorter than baseline values. Rats were pretreated by spinal microdialysis infusion of group I mGlu receptor antagonists, LY393053 [(±)-2-amino-2-(3-cis andtrans-carboxycyclobutyl-3-(9-thioxanthyl)propionic acid], LY367385 [(S)-(+)-α-amino-4-carboxy-2-methylbenzeneacetic acid], or AIDA [(R,S)-1-aminoindan-1,5-dicarboxylic acid/UPF 523] before knee joint injection.The paw withdrawal latencies measured 4 h after the injection were significantly longer in the presence of group I mGlu receptor antagonists than those of the artificial cerebrospinal fluid-treated arthritic control group. Post-treatment with the group I mGlu receptor antagonists LY367385 and AIDA allowed significant recovery of the paw withdrawal latencies after the onset of the knee joint inflammation. The knee joint inflammation itself was not affected by either treatment. The results of the present study indicate that secondary thermal hyperalgesia can be effectively attenuated during both the development and maintenance phases of acute knee joint inflammation by spinal application of specific group I mGlu receptor antagonists.

Footnotes

  • This study is supported by National Institutes of Health Grant RO1 32778 and a grant funded by the Sealy Endowment.

  • Abbreviations

    NMDA
    N-methyl-d-aspartate
    mGlu
    metabotropic glutamate
    LY393053
    (+)-2-amino-2-(3-cis andtrans-carboxycyclobutyl-3-(9-thioxanthyl)propionic acid
    LY367385
    (S)-(+)-α-amino-4-carboxy-2-methylbenzeneacetic acid
    AIDA
    (R,S)-1-aminoindan-1,5-dicarboxylic acid/UPF 523
    AMPA
    α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
    aCSF
    artificial cerebrospinal fluid
    • Received March 9, 2001.
    • Accepted September 28, 2001.
    • The American Society for Pharmacology and Experimental Therapeutics
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    Journal of Pharmacology and Experimental Therapeutics: 300 (1)
    Journal of Pharmacology and Experimental Therapeutics
    Vol. 300, Issue 1
    1 Jan 2002
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    Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

    Group I Metabotropic Glutamate Receptor Antagonists Block Secondary Thermal Hyperalgesia in Rats with Knee Joint Inflammation

    Liping Zhang, Ying Lu, Ying Chen and Karin N. Westlund
    Journal of Pharmacology and Experimental Therapeutics January 1, 2002, 300 (1) 149-156; DOI: https://doi.org/10.1124/jpet.300.1.149

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    Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

    Group I Metabotropic Glutamate Receptor Antagonists Block Secondary Thermal Hyperalgesia in Rats with Knee Joint Inflammation

    Liping Zhang, Ying Lu, Ying Chen and Karin N. Westlund
    Journal of Pharmacology and Experimental Therapeutics January 1, 2002, 300 (1) 149-156; DOI: https://doi.org/10.1124/jpet.300.1.149
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