NMDA receptor antagonists chronic pain

Eisenberg, E., Pud, D., 1998. Can patients with chronic neuropathic pain be cured by acute administration of the NMDA receptor antagonist amantadine . Pain 74, 337-339. 

By far the most evidence for an essential role of NMDA receptor activation especially in chronic pain has been provided by pharmacological studies with NMDA receptor antagonists which is discussed below. 

NMDA Receptor Antagonists for the Treatment of Chronic Pain. .. 253... 

Hewitt D. J. (2000). The use of NMDA-receptor antagonists in the treatment of chronic pain. Clin. J. Pain 16 S73-S79. 

Hs Weak noncompetitive NMDA-receptor antagonist (high doses), which may contribute to actions in chronic pain... 

The N-methyl-d-aspartate (NMDA) receptors are one of the main mediators of excitatory neurotransmission and through inhibition of NMDA receptors, which are thought to play a crucial role in the generation and maintenance of chronic pain, NMDA receptor antagonists can be administered to produce analgesia. The receptor is a ligand-gated ion channel, which permits the influx of calcium and sodium and the efflux of potas-... 

Chen SR, Samoriski G, Pan HI. Antinociceptive effects of chronic administration of uncompetitive NMDA receptor antagonists in a rat model of diabetic neuropathic pain. Neuropharmacology 2009 57 121-126. 

The high efficacy of amitriptyline in chronic pain may be in part related to an antagonistic action at NMDA receptors (Eisenach and Gebhart, 1995) (see Table 2). 

NMDA antagonist [56], has been studied in the treatment of acute and chronic pain [57]. The NMDA receptor has a crucial role in excitatory synaptic transmission, plasticity, and neurodegeneration in the central nervous system [58] and has become an avenue to modulate the excitatory effects of glutamate. 

Uncontrolled post-operative acute pain, particularly in patients with a history of chronic pain and opioid dependency, can be quickly and effectively relieved by careful and slow titration of intravenous methadone. Similar results maybe achieved in some opioid-naive patients who are refractory to high doses of potent opioids administered in the post-anesthesia care unit (PACU). This author uses 2.5 mg of methadone every 5-10 minutes to extinguish the fire associated with poorly controlled pain, and, once adequate analgesia is obtained, initiates hydromorphone intravenous PCA bolus with or without continuous infusion. It is likely that the intrinsic NMDA antagonistic property of the d-isomer of methadone blunts NMDA receptor activation and spinal sensitization induced by opioids (opioid hyperalgesia) as well as poorly controlled pain. 

---