Severe pain occurs in 5-30% of the spinal cord-injured (SCI) population and is difficult to treat. Subarachnoid lidocaine has been used in selected patients with some success. Mexiletine, an analog of lidocaine that acts at Na+/K+ channels in the peripheral nerve, has been found effective in persons with diabetic dysesthetic neuropathy. The effect of mexiletine in the treatment of spinal cord dysesthetic pain was examined in this study. Fifteen patients were enrolled, and 11 patients completed the prospective, randomized, placebo-controlled, double-blind, crossover design trial. Inclusion/exclusion criteria were carefully defined. A 1-wk washout period was followed by a 4-wk drug trial of either mexiletine (450 mg/day) or placebo. This was repeated for the second medication in the second arm of the study. Patients were followed weekly with McGill and visual analog pain scales. Baseline, midpoint, and endpoint Barthel function scores were recorded. The Wilcoxon's signed-rank test and paired t test were used for statistical analysis. Results showed no significant effect of mexiletine on SCI dysesthetic pain scales or Barthel index. In conclusion, in this trial, mexiletine did not appear to decrease spinal cord injury-related dysesthetic pain.