NMDA Receptor Antagonists in the Treatment of Pain

Over the past three decades, the central glutamatergic system, particularly the role of the N-methyl-d-aspartate (NMDA) receptor in the neural mechanisms of persistent pain, has been extensively investigated. Chronic pain can be sustained by way of a central sensitization process involving the NMDA receptor system. Data from preclinical studies have consistently supported a crucial role of the central glutamatergic system and NMDA receptors in the induction and maintenance of persistent pain resulting from pathological conditions such as inflammation and nerve injury. To date, clinical trials have resulted in mixed conclusions as to the overall effectiveness in treating persistent pain with NMDA receptor antagonists. Nonetheless, NMDA receptor antagonists have been demonstrated as an effective treatment option in the management of chronic pain, particularly for pain which has been refractory to other treatment modalities.