Unaltered pain-related behavior in mice lacking NMDA receptor GluRepsilon 1 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 GluRepsilon 2-containing NMDARs in pain mechanisms, the functional significance of GluRepsilon 1-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 GluRepsilon 1 subunit gene deletion on pain-related behavior in mice. In all of the models tested, GluRepsilon 1-deficient mice exhibited responses similar to wild-type controls. These results suggest that GluRepsilon 1 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 GluRepsilon 2-containing NMDARs could explain unaltered nociceptive behavior in mutant mice.
Petrenko
Andrei B
AB
Department of Cellular Neurobiology, Brain Research Institute, Niigata University, 1 Asahimachi-dori, Japan.
Yamakura
Tomohiro
T
Baba
Hiroshi
H
Sakimura
Kenji
K
D000818:Animals; D019771:Axotomy; D001522:Behavior, Animal / Q000502:physiology*; D015153:Blotting, Western; D005557:Formaldehyde / Q000494:pharmacology; D005620:Freund's Adjuvant / Q000494:pharmacology; D006614:Hindlimb / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D007509:Irritants / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009619:Nociceptors / Q000378:metabolism; D010146:Pain / Q000235:genetics* / Q000378:metabolism*; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology; D010812:Physical Stimulation; D011930:Reaction Time / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
D007509:Irritants; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D005557:Formaldehyde; D005620:Freund's Adjuvant