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Mechanically evoked intense itch without any pain-related sensory components in healthy human subjects provides direct evidence of mechanosensitive but nonnociceptive neurons involved in itch in humans.When a newly developed experimental method to vibrate vellus hairs on human skin was applied to the face and arm in healthy subjects, intense itch was reproducibly induced on the face, but not on the arm, without any flare reactions. In contrast to histamine-induced itch, mechanically evoked itch was not characterized as burning or stinging by any subjects, and was resistant to histamine H1-receptor antagonists. When the stimulation was continued for 10 min, mechanically evoked itch reached the maximum intensity within 10 s, but gradually attenuated after 60 to 90 s and was rarely perceivable at the end of stimulation. When the stimulation was discontinued at 90 s, mechanically evoked itch rapidly attenuated after the end of stimulation, but took more than 10 min before it completely diminished. These results indicate a possible involvement of C-tactile neurons in mechanically evoked itch because they have consistent characteristics such as low mechanical thresholds, intermediate adaptation, after discharge, favorable response to slowly moving stimuli, and fatigue during repeated mechanical stimulation, although it needs to be confirmed by future microneurographic studies. Touch-alloknesis was present in the adjacent skin area until mechanically evoked itch completely diminished, supporting the hypothesis that itch sensitization can be caused by a continuous activation of peripheral itch neurons whether or not they are histamine-sensitive C nerves. In conclusion, this study provides direct evidence of mechanosensitive nerves involved in itch in human skin. The purity of mechanically evoked itch without any pain-related sensory components is a major advantage for investigating the differentiation of itch from pain.