In our current clinical trial, we are comparing the effects of two NMDA receptor antagonists to placebo in patients with painful distal symmetrical diabetic neuropathy or post-herpetic neuralgia. The treatments in this three-period crossover study are dextromethorphan, up to 920 mg/day (about 8 times the antitussive dose), memantine, 30-50 mg/day, and placebo. Memantine is an NMDA antagonist used in Europe to treat Parkinson's disease and Alzheimer's disease. The underlying hypothesis, based on studies of painful neuropathies in animal models, is that neuropathic pain is caused largely by sensitization of central nervous system neurons caused by excitatory amino acid neurotransmitters, acting largely through NMDA receptors. A previous small trial of dextromethorphan suggested efficacy in diabetic neuropathy pain. The study requires one visit to the NIH outpatient Pain Research Clinic, and consists of three 9-week treatment periods. Patients who respond to one of the medications will be invited to participate in further controlled studies of the medication followed by up to several years of open-label treatment under continued observation.

In our current clinical trial, we are comparing the effects of two NMDA receptor antagonists to placebo in patients with painful distal symmetrical diabetic neuropathy or post-herpetic neuralgia. The treatments in this three-period crossover study are dextromethorphan, up to 920 mg/day (about 8 times the antitussive dose), memantine, 30-50 mg/day, and placebo. Memantine is an NMDA antagonist used in Europe to treat Parkinson's disease and Alzheimer's disease. The underlying hypothesis, based on studies of painful neuropathies in animal models, is that neuropathic pain is caused largely by sensitization of central nervous system neurons caused by excitatory amino acid neurotransmitters, acting largely through NMDA receptors. A previous small trial of dextromethorphan suggested efficacy in diabetic neuropathy pain. The study requires one visit to the NIH outpatient Pain Research Clinic, and consists of three 9-week treatment periods. Patients who respond to one of the medications will be invited to participate in further controlled studies of the medication followed by up to several years of open-label treatment under continued observation.

• Diabetic Neuropathies
• Herpes Zoster
• Neuralgia

• Albers GW, Saenz RE, Moses JA Jr, Choi DW. Safety and tolerance of oral dextromethorphan in patients at risk for brain ischemia. Stroke. 1991 Aug;22(8):1075-7.
• Bakshi R, Faden AI. Competitive and non-competitive NMDA antagonists limit dynorphin A-induced rat hindlimb paralysis. Brain Res. 1990 Jan 15;507(1):1-5.
• Choi DW. Dextrorphan and dextromethorphan attenuate glutamate neurotoxicity. Brain Res. 1987 Feb 17;403(2):333-6.

Patients must be over 18 years of age.

Patients must have a definite diagnosis of diabetic neuropathy or post herpetic neuralgia or a diagnosis of neuropathic pain of various etiologies other than diabetic neuropathy or post herpetic neuralgia.

Duration of symptoms must be at least 3 months.

Severity of pain must be at least mild, if constant; or at least moderate, if intermittent and at least 2 hours duration a day.

Patients using tricyclics, narcotics, or antiseizure medications, must keep the drug dosages constant throughout the study.

No patients with unstable disease process; i.e., angina pectoris, accelerated hypertension, recent stroke or transient cerebral ischemia, uncontrolled seizures.

No pregnant or lactating women. Women of child bearing potential must use birth control pills, intrauterine device, or barrier contraceptive devices.

No history of significant drug abuse or PCP use. No history of IV drug abuse, prescription drug abuse, or alcoholism.

No significant liver or kidney disease.

No MAO inhibitors.

No cognitive impairment or language difficulty as judged by difficulty completing pain diary, medical history, or telephone conversation.

Patients must not have any other chronic pain condition that gives them pain greater than the neuropathy pain.