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

  • Eur J Pharmacol. 2008 Feb 12;580(3):314-21. doi: 10.1016/j.ejphar.2007.09.047.
Chang Z Zhu  1 ,  Scott Baker ,  Odile EI-Kouhen ,  Sonya G Lehto ,  Peter R Hollingsworth ,  Donna M Gauvin ,  Gricelda Hernandez ,  GuoZhu Zheng ,  Renjie Chang ,  Robert B Moreland ,  Andrew O Stewart ,  Jorge D Brioni ,  Prisca Honore
Affiliations
  • 1. Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-3500, USA. [email protected]
PMID: 18054908 DOI: 10.1016/j.ejphar.2007.09.047
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.

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