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

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.

Wound pruritus: pathophysiology and management

“…34 The multidimensionality of itch is indicated as multiple areas of the brain are activated when itch is induced. Drzezga et al 35 used PET scanning to study the central processing of histamine-induced itch. They noted significant activation of contralateral somatosensory cortex, as well as contralateral and ipsilateral motor areas, but no thalamic activation.…”

TRP Channels and Pruritus

“…Beyond these regions, alterations in neuronal activities in several brain areas were reported in relation to itch processing above the thalamus; these include the primary and secondary somatosensory cortex, the premotor and supplementary motor cortex, the inferior parietal lobe, the cerebellum as well as certain temporal regions [34][35][36][37][38][39][40]. Although there are slight variations in the itch-related regions reported among studies, which could be due to different experimental designs [40], there is a consensus in the literature about the following: (i) the sensory-discriminative component of itch is likely processed in the primary somatosensory cortex; (ii) the activities of the anterior cingulate and insular cortex may be related to the motivational and affective components; (iii) the motor component of the goal-directed scratching is attributed to the premotor and supplementary motor areas; (iv) these brain regions are also involved in the central pain processing; therefore, distinction of the two sensations is mainly based on the differential activation patterns of mostly identical centers [4, 10, 35-37, 41, 42].…”

Pruritus intensity assessment: challenge for clinicians

“…Several studies have revealed that brain processing of itchy stimuli in patients with chronic pruritus differs from that observed in healthy controls [34][35][36]. Thus, it could be suggested that mapping of brain activity during itch episodes may provide valuable information helping in the assessment of the degree of itch intensity.…”

“…However, current data are rather preliminary, as there is great variability in currently achieved results with different diagnostic techniques. These methods are also too expensive to be used as a routine diagnostic procedure, and thus they are used only for scientific purposes to better understand what happens within the brain upon itchy stimuli [34][35][36].…”