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Activation of metabotropic glutamate receptor 7 in spinal cord inhibits pain and hyperalgesia in a novel formalin model in sheep.

  This study set out to characterize the contribution of group III metabotropic glutamate receptor 7 activation to nociceptive behaviour and mechanical hypersensitivity in a novel formalin test in sheep. The mGlu receptor 7 allosteric agonist, N,N′-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN082; 2–20 mM), the nonselective group III mGlu receptor agonist L-(+)-2-amino-4-phosphonobutyric acid (0.2–20 mM) and drug vehicle were injected intrathecally into naive subjects (n=7 per group), or 5 min preformalin (3%; 0.2 ml)/saline injection (intradermal), into the lower forelimb of adult female sheep (n=5–7 per group). Forelimb withdrawal thresholds to noxious mechanical stimulation and pain behaviours (time spent nonweight bearing or flinching) were assessed for up to 180 min. Formalin induced a characteristic biphasic pain–behaviour response and mechanical hyperalgesia between 1–5 and 30–120 min postinjection. Treatment with AMN082, but not L-(+)-2-amino-4-phosphonobutyric acid significantly inhibited both early and late phase formalin-induced hyperalgesia and pain behaviours. AMN082 also induced a rapid but short lasting analgesia in naive subjects. These data suggest that enhancing endogenous metabotropic glutamate receptor 7 activity in spinal cord, using the novel allosteric modulator, AMN082, blocks pain and hyperalgesia, and may be of therapeutic benefit for the treatment of inflammatory pain.

  • Type:

    Article

  • Date:

    30 November 2010

  • Publication Status:

    Published

  • Publisher

    Lippincott, Williams & Wilkins

  • DOI:

    10.1097/FBP.0b013e3283478802

  • ISSN:

    0955-8810

  • Library of Congress:

    RM Therapeutics. Pharmacology

  • Dewey Decimal Classification:

    615 Pharmacology and therapeutics

Citation

Dolan, S., Gunn, M. D., Crossan, C. & Nolan, A. M. (2010). Activation of metabotropic glutamate receptor 7 in spinal cord inhibits pain and hyperalgesia in a novel formalin model in sheep. Behavioural Pharmacology. 22, 582-588. doi:10.1097/FBP.0b013e3283478802. ISSN 0955-8810

Authors

Keywords

AMN082; formalin; formalin test; hyperalgesia; metabotropic glutamate receptor 7; mGlu7 receptor agonist; pain; sheep;

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