Central activation by histamine-induced itch: analogies to pain processing: a correlational analysis of O-15 H2O positron emission tomography studies

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Abstract
The aim of this study was to identify the functional cerebral network involved in the central processing of itch and to detect analogies and differences to previously identified cerebral activation patterns triggered by painful noxious stimuli. Repeated positron emission tomography regional cerebral blood flow (rCBF) measurements using O15-labeled water were performed in six healthy right-handed male subjects (mean age 32 +/- 2 years). Each subject underwent 12 sequential rCBF measurements. In all subjects a standardized skin prick test was performed on the right forearm 2 min before each rCBF measurement. For activation, histamine was applied in nine tests in logarithmically increasing concentrations from 0.03 to 8%. Three tests were performed with isotonic saline solution serving as a control condition. Itch intensity and unpleasantness were registered with a visual analogue scale during each test. Subtraction analysis between activation and control conditions as well as correlation analysis with covariates were performed. Itch induced a significant activation in the predominantly contralateral somatosensory cortex and in the ipsilateral and contralateral motor areas (supplementary motor area (SMA), premotor cortex, primary motor cortex). Additional significant activations were found in the prefrontal cortex and the cingulate gyrus, but not in subcortical structures nor in the secondary somatosensory cortex. In correlation analyses, several cortical areas showed a graded increase in rCBF with the logarithm of the histamine concentration (bilateral sensorimotor areas and cingulate cortex; contralateral insula, superior temporal cortex and prefrontal cortex) and with itch unpleasantness (contralateral sensorimotor cortex, prefrontal cortex and posterior insula; ipsilateral SMA). Induction of itch results in the activation of a distributed cerebral network. Itch and pain seem to share common pathways (a medial and a lateral processing pathway and a strong projection to the motor system). In contrast to pain activation studies, no subcortical (i.e. thalamic) activations were detected and correlation analyses suggest differences in subjective processing of the two sensations.