N-methyl-D-aspartate (NMDA) receptors are involved in the development of central sensitization associated with chronic refractory pain syndromes.
NMDA antagonists may modulate the CNS function, offering a novel approach to the treatment of chronic pain. Some studies suggest that ketamine, administered by intravenous infusion or orally, may be effective in relieving pain. However, intravenous ketamine may induce serious side effects such as vivid hallucination and psychosis. Recent reports suggest low dose ketamine may offer effective pain relief with remarkably few side effects.
Methadone has the property of both opioid receptor agonist and MNDA antagonist.
There is evidence indicating that methadone is an analgesic with similar efficacy to morphine. Non-controlled clinical studies have demonstrated that methadone has a particular role in neuropathic pain. However, adverse effects due to prolonged half-life, particularly respiratory depression and death, make it critical for providers to be familiar with methadone’s pharmacological properties before considering methadone as an analgesic therapy for chronic pain. Amantadine is a noncompetitive NMDA antagonist.
Memantine is an NMDA antagonist used for the treatment of Alzheimer’s disease. Both of these medications possess some analgesic properties. Current data is too scant, however, to recommend clinical use in chronic pain management. Recent studies show that a combination oral medication producing high blood levels of dextromethorphan may decrease neuropathic pain due to trauma and phantom limb pain.