Significant differences in central imaging of histamine-induced itch between atopic dermatitis and healthy subjects.
ABSTRACT This is the first investigation of the central processing of itch in the brain in 8 subjects with atopic dermatitis (AD) in comparison to 6 healthy controls (HC), comparing histamine-induced itch related activations in the frontal, prefrontal, parietal, cingulate cortex, thalamus, basal ganglia and cerebellum.
We employed 1% histamine-dihydrochlorid-iontophoresis of the left hand, recorded H2(15)O-PET-scans and perception of itch intensity on a numeric rating scale.
There was no significant difference in perceived itch intensity between AD and HC. Significant increase in rCBF was found in HC in the contralateral somatosensory and motor cortex, midcingulate gyrus, and ipsilateral prefrontal cortex; in AD: in the contralateral thalamus, somatosensory, motor and prefrontal cortex and cerebellum, in the ipsilateral precentral, prefrontal, orbitofrontal cortex, insula, pallidum and cerebellum. More brain sites were activated in AD than in HC. Activation in AD was significantly higher in the contralateral thalamus, ipsilateral caudate and pallidum.
We interpret our findings as possible central correlates of changes in the motor system in subjects with chronic itch, with activation of the basal ganglia possibly correlating to the vicious itch-scratch-circle in subjects with chronic itching skin diseases. However, further neuroimaging studies in healthy subjects and also in different skin diseases are needed to understand the complex mechanisms of the processing of itch.
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ABSTRACT: Previous PET and fMRI brain imaging studies targeting neural networks processing itch sensation have used histamine as the sole itch inducer. In contrast with histamine, cowhage-induced itch is mediated via proteinase activated receptors PAR2 and is transmitted through a separate spinothalamic pathway, therefore imaging the brain activation evoked by cowhage could provide further insight into central processing of itch. We report for the first time a functional MRI Arterial Spin Labeling (ASL) study of neuronal processing of itch induced by cowhage, analyzed in contrast with histamine-induced itch. We also explored the brain responses induced by histamine and cowhage combined in a tight sequence. The results of our analyses obtained in a group of 15 healthy volunteers suggested that cowhage and histamine co-activated a core group of brain structures, while also revealing notable differences. Core areas activated by both stimuli were found in the thalamus, primary and secondary somatosensory cortices, posterior parietal cortex, superior and middle temporal cortices, PCC, ACC, precuneus and cuneus. Cowhage induced a notably distinct and more extensive involvement of the insular cortex, claustrum, basal ganglia, putamen, thalamic nuclei and pulvinar. The differences observed between these two itch modalities were investigated to determine the impact of quantitative versus qualitative factors, and correlations between itch intensity and the patterns in brain activation were explored. Our analysis revealed that the most significant differences between cowhage and histamine itch were not affected by stimulus intensity, although a subset of regions displayed activations which were intensity-dependent. The combined application of cowhage and histamine highlighted the role of insula and claustrum in the processing of both itch modalities in the same time. The present results suggest the existence of overlapping but also distinct neuronal networks processing these two different types of itch.NeuroImage 11/2011; 59(4):3611-23. DOI:10.1016/j.neuroimage.2011.10.099 · 6.13 Impact Factor
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ABSTRACT: I tching (pruritus) is perhaps the most common symptom associated with numerous skin diseases and can be a lead symptom of extracutaneous disease (e.g., malignancy, infection, metabolic dis‑ orders). Also in atopic dermatitis itching sensations constitute one of the most prominent and distressing features. However, the most characteristic response to itching is the scratch reflex: a more or less voluntary, often sub‑conscious motor activity, to counteract the itch by slightly painful stimuli. The benefit of a short‑termed relieve from itching through this scratch reflex though is counteracted by a simultaneous damage of the epidermal layer of the skin which leads to increased transepidermal water loss and drying, which in turn results in a cycle of more itching and more scratching. A be‑ wilderingly wide range of peripheral itch‑inducing stimuli generated within or administered to the skin are able to trigger pruritus, one of them being histamine. Based on early experiments, histamine has been suggested to may play a key role in the pathogenesis of AD. This is reflected by a history for antihistamines in the therapeutic medication of AD patients. Antihistamines are believed to share a common antipruritic effect and therefore are prescribed to almost any AD patient suffering from itch to act alleviating. This general assumption has been proved to be wrong. To assess the benefit of antihistamines in the treatment of AD in a better way, their mechanisms and specific effects need to be understood more precisely. In particular their precise indication is crucial for successful use. This book chapter will therefore summarize and assess the role of histamine in AD and the efficacy of antihistamines in its treatment based on results of basic research and clinical studies.Journal of Dermatological Treatment 01/1991; 1(6). · 1.76 Impact Factor
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ABSTRACT: The aim of this study was to examine the effects of glafenine hydrochloride (a nonsteroidal anti-inflammatory drug) on proliferation, clonogenic activity, cell-cycle, migration, and the extracellular matrix protein tenascin of human aortic smooth muscle cells (haSMCs) and human endothelial cells (ECs) in vitro.HaSMCs and ECs were seeded in tissue culture flasks. The cells were treated for 4 days with glafenine hydrochloride (10 microM, 50 microM, 100 microM). Half of the treated groups were incubated again with glafenine hydrochloride, the other half received medium free of glafenine hydrochloride every 4 days until day 20. The growth kinetics and clonogenic activity were assessed. Cell cycle distribution was investigated by FACS, migratory ability was evaluated, and effects on extracellular matrix synthesis were assessed by immunofluorescence. Glafenine hydrochloride inhibited the proliferation and clonogenic activity of haSMCs and ECs in a dose-dependent manner. A block in the G2/M phase and a reduction in the G1 phase occurred. The migratory ability of haSMCs was impaired in a dose-dependent manner and the extracellular matrix protein tenascin was reduced. As glafenine hydrochloride has the ability to fully inhibit proliferation and to partially inhibit migration in haSMCs, it could be an interesting substance for further research in the field of restenosis therapy.Cell Biology International 02/2003; 27(12):987-96. · 1.64 Impact Factor