Significant differences in central imaging of histamine-induced itch between atopic dermatitis and healthy subjects

Department of Psychosomatics and Psychotherapy, University of Münster, Domagkstr. 22, D-48149 Münster, Germany.
European journal of pain (London, England) (Impact Factor: 2.93). 02/2008; 12(7):834-41. DOI: 10.1016/j.ejpain.2007.12.003
Source: PubMed


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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    • "The brain activation evoked by the stimulation of these two itch pathways overlapped to a substantial extent, while in the same time presented distinguishable particularities (Figure 2). The pattern of brain activation observed for histamine itch was in agreement with previous results reported in the literature (Hsieh et al, 1994; Darsow et al, 2000; Drzezga et al, 2001; Mochizuki et al, 2003, 2009; Leknes et al, 2007; Schneider et al, 2008); however, we also found significant activations in the thalamus and in the primary and secondary somatosensory areas which were reported before, but not consistently. "
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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.
    Full-text · Article · Nov 2011 · NeuroImage
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    • "Neuroimaging studies on itch have been done using [15O]H2O-PET[6,12,15,16,20] and, more recently, fMRI[17-21]. Table 1 summarizes their findings. "
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    ABSTRACT: Itch is the major symptom of many allergic or inflammatory skin diseases, yet it is still difficult to measure objectively. This article shows and updates the development and approaches of central nervous system investigation of itch. Human neuroimaging studies on the physiology and pathophysiology of itch sensation have been hampered by the lack of a reproducible "on-off" stimulus. Short-term alternating temperature modulation of histamine-induced itch has recently been shown to provide on-off characteristics. Recent studies with functional magnetic resonance imaging demonstrate that itch sensation in healthy volunteers is processed by a network of brain regions contributing to the encoding of sensory, emotional, attentional, evaluative, and motivational aspects of itch.
    Full-text · Article · Oct 2008 · World Allergy Organization Journal
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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.
    Full-text · Article · Jan 1991 · Journal of Dermatological Treatment
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