Novel approaches to targeting glutamate receptors for the treatment of chronic pain: review article.

Glutamatergic mechanisms are implicated in acute and chronic pain, and there is a great diversity of glutamate receptors that can be used as targets for novel analgesics. Some approaches, e.g. NMDA receptor antagonism, have been validated clinically, however, the central side-effects have remained the main problem with most compounds. Recently, some novel approaches have been explored as new compounds targeting some modulatory sites at the NMDA receptor (glycine(B) and NR2B-subtype selective antagonists), as well as kainate and metabotropic glutamate receptors, have been discovered. Many of these compounds have demonstrated efficacy in animal models of chronic pain, and some of them appear to have a reduced side-effect liability compared to clinically tested NMDA antagonists. These recent advances are reviewed in the present work.