Unaltered pain-related behavior in mice lacking NMDA receptor GluRε1 subunit

Noxious afferent input following tissue damage and inflammation triggers a state of neuronal hyperexcitability-a phenomenon of central sensitization-which manifests behaviorally as allodynia and hyperalgesia. At the molecular level, maintenance of central sensitization is largely dependent on the N-methyl-D-aspartate receptor (NMDAR) activation. NMDARs are composed of GluRzeta1 (NR1) and one of four GluRepsilon (NR2) subunits, which determine the functional properties of native NMDARs. Although there is accumulating evidence to implicate. GluRepsilon2-containing NMDARs in pain mechanisms, the functional significance of GluRepsilon1-containing NMDARs in this setting has not been examined in detail. Here, we used hind paw injection of formalin, complete Freund's adjuvant and a nerve injury model to investigate the effects of GluRepsilon1 subunit gene deletion on pain-related behavior in mice. In all of the models tested, GluRepsilon1-deficient mice exhibited responses similar to wild-type controls. These results suggest that GluRepsilon1 disruption does not result in altered nociceptive behavior in mice. Although the contribution of other nociceptive pathways cannot be ruled out, we speculate that the preserved function of GluRepsilon2-containing NMDARs could explain unaltered nociceptive behavior in mutant mice. (C) 2003 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.