Dextromethorphan reduces some aspects of FM pain

Janis Kelly

June 08, 2005

June 8, 2005

Gainesville, FL - Temporal summation of repeated pain stimuli, also known as "windup" pain, is mediated by N-methyl-D-aspartate (NMDA) receptors, and this pathway has long been suspected of contributing to the abnormal pain responses seen in some fibromyalgia (FM) patients. Dr Roland Staud (University of Florida, Gainesville) reports in the May 2005 issue of the Journal of Pain that at least one aspect of NMDA function remains normal in FM patients: the receptors can be blocked by the centrally acting NMDA-receptor antagonist dextromethorphan, a compound commonly used in over-the-counter cough remedies [ 1 ].

"Our results provide evidence that dextromethorphan could be clinically effective for FM, particularly in combination with other agents that act peripherally to reduce sensitization of nociceptors," Staud writes.

Preventing "windup" pain

Dextromethorphan could be clinically effective for FM, particularly in combination with other agents that act peripherally to reduce sensitization of nociceptors.

Dextromethorphan reduces coughing by elevating the threshold for the NMDA-mediated cough reflex. Staud suggests that the drug be explored as a treatment for fibromyalgia because it also reduces certain aspects of FM pain.

"I think it's one piece of the mosaic," Staud says. "We currently have no single therapy in chronic pain that has a big effect. So what this really means for chronic pain patients is that they need to use a whole host of different interventions to decrease the pain they have. And in this, dextromethorphan may have a role in the future."

Staud tested the effects of dextromethorphan on windup pain in two studies. The first measured the effect of dextromethorphan vs placebo in 10 normal female and 10 normal male subjects. The second tested the effect of dextromethorphan vs placebo on windup pain in 10 female normal controls and 14 female FM patients.

Thermal windup pain was produced by computer-controlled heat stimulation of the skin. Mechanical windup pain was tested by repetitive mechanical stimulation of the adductor pollicis muscle of either hand.

Patients were given capsules containing 0, 60, or 90 mg of dextromethorphan 1.5 hours before testing.

Compared with placebo, the 90-mg dextromethorphan dose, but not the lower doses, significantly reduced thermal windup pain in male and female normal control subjects and in female FM subjects. Compared with placebo, both 60-mg and 90-mg dextromethorphan doses significantly reduced mechanical windup pain in male and female normal controls and in female FM subjects. (The usual dextromethorphan dose for cough suppression is 10 to 20 mg every four to eight hours.)

"Female subjects clearly exhibited enhanced pain sensitivity. . . . However, oral dextromethorphan produced similar reductions in thermal and mechanical windup pain for female normal controls and FM subjects. Thus, the central NMDA-receptor systems of FM subjects are more responsive to thermal and mechanical stimulation but are not differentially sensitive to NMDA-receptor antagonism," Staud reported.

The investigators concluded that although central sensitization is the hallmark of most FM patients, pain-processing mechanisms other than NMDA-receptor mechanisms must be involved, since those mechanisms are not much different from normal controls in FM subjects.

Staud warns that FM patients should not start dosing themselves with cough syrup. "Like every medication, dextromethorphan has side effects," he said. "At high doses, patients can have problems related to memory and confusion."


  1. Staud R, Vierck CJ, Robinson ME, et al. Effects of the N-methyl-D-aspartate receptor antagonist dextromethorphan on temporal summation of pain are similar in fibromyalgia patients and normal control subjects. J Pain 2005; 6:323-332.



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