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

Dolan, Sharron; Gunn, Mark Donald; Crossan, Claire; Nolan, Andrea M

Abstract

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.

Citation

Dolan, S., Gunn, M. D., Crossan, C., & Nolan, A. M. (2011). 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. https://doi.org/10.1097/FBP.0b013e3283478802

• Journal Article Type: Article
• Publication Date: 2011
• Deposit Date: Mar 27, 2014
• Journal: Behavioural Pharmacology
• Print ISSN: 0955-8810
• Electronic ISSN: 1473-5849
• Publisher: Lippincott, Williams & Wilkins
• Peer Reviewed: Peer Reviewed
• Volume: 22
• Pages: 582-588
• DOI: https://doi.org/10.1097/FBP.0b013e3283478802
• Keywords: AMN082; formalin; formalin test; hyperalgesia; metabotropic glutamate receptor 7; mGlu7 receptor agonist; pain; sheep
• Public URL: http://researchrepository.napier.ac.uk/id/eprint/6684
• Publisher URL: http://dx.doi.org/10.1097/FBP.0b013e3283478802