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Eur J Pharmacol. 2008 Feb 12;580(3):314-21. Epub 2007 Nov 13.

Analgesic activity of metabotropic glutamate receptor 1 antagonists on spontaneous post-operative pain in rats.

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1
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-3500, USA. Chang.Z.Zhu@abbott.com

Abstract

Activation of metabotropic glutamate (mGlu) receptors has previously been shown to play a role in inflammatory or neuropathic pain states. However, the role of mGlu type 1 receptors in post-operative pain remains to be investigated. In the present study, effects of potent and selective mGlu1 receptor antagonists A-841720, A-794282, A-794278, and A-850002 were evaluated in a skin incision-induced post-operative pain model in rats. Post-operative pain was examined 2 h following surgery using weight-bearing difference between injured and uninjured paws as a measure of spontaneous pain. In this model, A-841720, A-794282, A-794278, and A-850002 induced significant attenuation of spontaneous post-operative pain behavior, with ED50s of 10, 50, 50, and 65 micromol/kg i.p., respectively. Depending on the compound, significant motor side effects were also observed at 3 to 10 fold higher doses. These results support the notion that mGlu1 receptor activation plays a significant role in nociceptive transmission in post-operative pain, though motor impairment may be a limiting factor in developing mGlu1 receptor antagonists as novel analgesics.

PMID:
18054908
DOI:
10.1016/j.ejphar.2007.09.047
[Indexed for MEDLINE]

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