The selective metabotropic glutamate receptor 7 allosteric agonist AMN082 inhibits inflammatory pain-induced and incision-induced hypersensitivity in rat

This study characterized the contribution of metabotropic glutamate receptor 7 (mGlu(7) receptor) activation to the development of inflammatory hyperalgesia and allodynia, using a novel, systemically active mGlu(7) receptor allosteric agonist, N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN082). The effects of AMN082 (0.1, 1 or 5 mg/kg, intraperitoneally; 5 or 50 nmol, intrathecally) or dicloferac (5 mg/kg, intraperitoneally) administered 30 min preprocedure or 3h postprocedure on hindpaw withdrawal latency (in seconds) to thermal stimulation, and response threshold (in grams) to mechanical stimulation, were measured in adult rats (n=6-8 per group) before and up to 24 h after intradermal injection of carrageenan into the hindpaw or hindpaw incision. Precarrageenan injection of 1 and 5 mg/kg AMN082, but not diclofenac inhibited thermal hyperalgesia, whereas postcarrageenan, both AMN082 and diclofenac attenuated thermal hyperalgesia and allodynia. In the paw incision model, presurgical and postsurgical administration of 1 and 5 mg/kg AMN082 inhibited thermal hyperalgesia, but not allodynia, whereas diclofenac was effective in attenuating both thermal hyperalgesia and allodynia but only when administered postsurgically. Intrathecal injection of AMN082 postcarrageenan and postsurgery also significantly attenuated thermal hyperalgesia. Enhancing endogenous mGlu(7) receptor activity inhibits postinjury stimulus-evoked hypersensitivity and may be of therapeutic benefit for the treatment of inflammatory and incision-induced pain. Behavioural Pharmacology 20:596-604 (c) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.