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.

The subjective sensation of itch is a complex emotional experience depending on a variety of factors. In this study, the central nervous processing of pruritus was investigated in a human model. Activation of involved cerebral areas was correlated to scales of nociception and skin reactions. Six healthy male right-handed subjects participated in a standardized epidermal stimulus model with nine increasing doses of histamine dihydrochloride (0.03%-8%) on their right forearms. Controls consisted of three NaCl stimuli. Cerebral activation patterns were determined by H(2)(15)O positron emission tomography 120 s after stimulation. Dermal reactions to the stimulus (wheal, flare, temperature) were coregistered during the procedure. Itch sensation was determined by visual analog scale rating. Pain was not reported during the study; all volunteers had localized itch from 0.03% histamine on. Subtraction analysis versus control revealed significant activation of the left primary sensory cortex and motor-associated areas (mainly primary motor cortex, supplementary motor area, premotor cortex). Predominantly left-sided activations of frontal, orbitofrontal, and superior temporal cortex and anterior cingulate were also observed. Correlation analysis revealed coactivation of dermal reactions 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, areas 2-5 (left); temperature, area 10 (left) and left insula. Itch intensity ratings were mainly correlated with activation of the left sensory and motor areas. Functional covariates of the itch sensation in the central nervous system were identified. The intention to pruritofensive movements is probably 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.J Invest Dermatol 115:1029-1033 2000

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The aim of this study was to use time-resolved functional magnetic resonance imaging (fMRI) to investigate temporal differences in the activation of the supplementary motor area (SMA) and the primary motor cortex (M1). We report data from eight human volunteers who underwent fMRI examinations in a 1.5T Philips Gyroscan ACS-NT MRI scanner. While wearing a contact glove, subjects executed a complex automated sequence of finger movements either spontaneously or in response to external auditory cues. Based on the result of a functional scout scan, a single slice that included the M1 and the SMA was selected for image acquisition (echo planar imaging, repetition time 100 ms, echo time 50 ms, 64 x 64 matrix, 1,000 images). Data were analyzed with a shifting cross-correlation approach using the STIMULATE program and in-house programs written in Interactive Data Language (IDL(TM)). Time-course data were generated for regions of interest in the M1 as well as in the rostral and caudal SMA. Mean time between onset of the finger movement sequence and half-maximum of the signal change in M1 was 3.6 s for the externally cued execution (SD 0.5) and 3.5 s for the spontaneous execution (SD 0.6). Activation in the rostral section of the SMA occurred 0.7 s earlier than it did in the M1 during the externally cued execution and 2.0 s earlier during the spontaneous execution, a difference significant at the P < 0.01 level. Our results indicate that rostral SMA activation precedes M1 activation by varying time intervals in the sub-second range that are determined by the mode of movement initialization. By applying a paradigm that exerts a differential influence on temporal activation, we could ensure that the observed timing differences were not the result of differences in hemodynamic response function.