Processing of histamine-induced itch in the human cerebral cortex: A correlation analysis with dermal reactions

The subjective sensation of itch is a complex emotional experience dependin g on a variety of factors. In this study, the central nervous processing of pruritus was investigated in a human model. Activation of involved cerebra l areas was correlated to scales of nociception and skin reactions. Six hea lthy male right-handed subjects participated in a standardized epidermal st imulus model with nine of histamine dihydrochloride (0.03%-8%) on their rig ht forearms, Controls consisted of three NaCl stimuli. Cerebral activation patterns were determined by (H2O)-O-15 positron emission tomography 120s af ter stimulation. Dermal reactions to the stimulus (wheal, flare, temperatur e) were coregistered during the procedure. Itch sensation was determined by visual analog scale rating. Pain was not reported during the study; all vo lunteers had localized itch from 0.03% histamine on. Subtraction analysis v ersus control revealed significant activation of the left primary sensory c ortex and motor-associated areas (mainly primary motor cortex, supplementar y motor area, premotor cortex). Predominantly left-sided activations of fro ntal, orbitofrontal, and superior temporal cortex and anterior cingulate we re also observed. Correlation analysis revealed coactivation of dermal reac tions and cerebral response to itch in the following Brodmann areas with a Z score greater than 5: wheal, areas 5 (bilateral) and 19 (right); flare, a reas 2-5 (left); temperature, area 10 (left) and left insula, Itch intensit y ratings were mainly correlated with activation of the left sensory and mo tor areas, Functional covariates of the itch sensation in the central nervo us system were identified. The intention to pruritofensive movements is pro bably mirrored by the activation of motor areas in the cortex, Other areas may be involved in emotional processing of sensations. Skin reactions wheal and flare also had significantly activated covariate areas in the central nervous system.