Lack of efficacy of topical capsaicin in serotonin-induced itch

Capsaicin (CAP) has been demonstrated to be an effective topical inhibitor of cutaneous vasodilatation, pain and pruritus induced by a variety of chemical and physical stimuli. In a previous study, we showed a significantly inhibitory effect of topical CAP treatment on histamine-induced itch and cutaneous vascular reactions in healthy subjects compared to atopic eczema patients. As serotonin is proposed to play a pathophysiological role in some types of pruritus (e.g. uremic and hepatic pruritus) and CAP has been described to be successful in hemodialysis-related pruritus, we investigated the antipruritic effect of topical CAP on serotonin-induced reactions in 10 healthy volunteers in comparison to untreated skin (UPS) and placebo substance (vehicle)-treated skin (VS). On the first day, serotonin iontophoresis was performed in untreated skin. One week later, the treatments started, using either CAP 0.05% liniment or a placebo liniment (vehicle) 3 times daily over a 5-day period. On day 6, serotonin was applied by iontophoresis within the pretreated skin. After another 1-week break, the treatments were performed vice versa on the corresponding infrascapular region. Weal and flare areas were planimetrically evaluated. Itch sensations were documentated by the volunteer on a scale over a 24-min follow-up period. The examination also comprised alloknesis, which stands for induction of perifocal sensations by usually non-itching stimuli. In CAP-treated skin, serotonin-induced wheals were significantly larger post-application compared to non-pretreated skin. Wheals were significantly larger in VS than in UPS. Comparison of serotonin-induced flares in the different study arms did not reveal any significant differences. Itch sensations were not significantly reduced by topical CAP application. The areas of alloknesis were smaller in capsaicin-treated skin compared to VS and UPS, but did not reach significant value. In conclusion, topical CAP application is not effective in serotonin-induced itching in healthy volunteers. Serotonin is most unlikely to play a role in the mechanism of action of CAP.