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The tricyclic antidepressants are often used for the treatment of neuropathic pain. In this study, we evaluated one of these drugs on human cutaneous experimental pain. A randomized, double-blinded, placebo-controlled, crossover design methodology was conducted. Subjects participated in 2 14-day study sessions separated by a 7-day washout period. One session was with desipramine and one with placebo. At baseline, Day 7, and Day 15, quantitative sensory testing was performed to thermal and mechanical stimuli. On Day 15 only, intradermal capsaicin was injected on the volar aspect of the forearm followed by an assessment of pain and hyperalgesia. Oral desipramine had no significant effect on acute sensory thresholds, pain, secondary hyperalgesia, or flare response induced by intradermal capsaicin. Mean peak plasma levels of desipramine were within the therapeutic range for the treatment of depression. This study further supports a lack of effect of the tricyclic antidepressants on acute nociception and experimentally-induced secondary hyperalgesia.