The role of N-methyl-D-aspartate (NMDA) receptors in pain: a review.

There is accumulating evidence to implicate the importance of N-methyl-D-aspartate (NMDA) receptors to the induction and maintenance of central sensitization during pain states. However, NMDA receptors may also mediate peripheral sensitization and visceral pain. NMDA receptors are composed of NR1, NR2 (A, B, C, and D), and NR3 (A and B) subunits, which determine the functional properties of native NMDA receptors.

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.