Naloxone increases pain induced by topical capsaicin in healthy human volunteers

&NA; Opioid receptors occur in locations of strategic importance within the central nervous system for modulation of pain. Is pain reduced by ongoing inhibition mediated by activation of these receptors? Experiments to date in which the opioid‐receptor antagonist, naloxone, is administered during a painful event have yielded unclear results. Topically applied capsaicin can be used to induce tonic pain of moderate to severe intensity without tissue injury and is an ideal stimulus for studying acute pain modulation. We therefore conducted a placebo‐controlled double‐blind crossover study to investigate the effects of naloxone on capsaicin‐induced pain (five men, four women, aged 29±5 years). Capsaicin (10%) was applied topically and subjects rated pain every 2 min. The subjects were told that any drug given to them could increase, decrease, or not change their pain sensation. Pain plateaued after 20 min. At 26 min subjects received either naloxone or placebo in double‐blind fashion. At 56 min subjects received the alternative (placebo or naloxone). In a second session the order of presentation was reversed. The naloxone induced a significant increase in pain compared both to baseline (P<0.01) and placebo (P<0.01). The peak effect, reached at 12–20 min after naloxone delivery, was 59% greater than placebo. This experiment suggests that acute pain is actively suppressed by endogenous opioid‐receptor activation.

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