Scratching evokes a rewarding and pleasurable sensation, particularly in chronic itch patients. To date, no study has investigated the cerebral activity during scratching in chronic itch patients and whether it differs from that in healthy subjects. Using arterial spin labeling functional magnetic resonance imaging, we analyzed and compared the cerebral mechanism of self-scratching and its correlation with pleasurability in 10 patients with chronic itch and in 10 healthy controls. Cowhage was applied to the right forearm to induce itch. Scratching significantly attenuated the itch sensation (P<0.001) and evoked an associated pleasurability. Scratching-induced pleasurability significantly activated the reward system in the chronic itch and healthy groups, confirming that this reward system has a crucial role in scratching-induced pleasurability. A higher activity during scratching in chronic itch patients, versus healthy controls, was noted in brain regions related to motor control and motivation to act, including the supplementary motor area, premotor cortex, primary motor cortex, and midcingulate cortex, as well as the caudate nucleus involved in the reward system. This overactivity may be associated with the addictive scratching and/or neural hypersensitization.