Dolan, S., Gunn, M.D., Crossan, C. and 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(5-6), pp. 582-588. (doi: 10.1097/FBP.0b013e3283478802) (PMID:21597362)
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Publisher's URL: http://dx.doi.org/10.1097/FBP.0b013e3283478802
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.
| Item Type: | Articles |
|---|---|
| Keywords: | AMN082, formalin, formalin test, hyperalgesia, metabotropic glutamate receptor 7, mGlu7 receptor agonist, pain, sheep |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Nolan, Professor Andrea and Gunn, Mr Mark |
| Authors: | Dolan, S., Gunn, M.D., Crossan, C., and Nolan, A.M. |
| Subjects: | R Medicine > RM Therapeutics. Pharmacology |
| College/School: | College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine |
| Journal Name: | Behavioural Pharmacology |
| ISSN: | 0955-8810 |
| ISSN (Online): | 1473-5849 |
| Related URLs: |
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