Processing of Histamine-Induced Itch in the Human Cerebral Cortex: A Correlation Analysis with Dermal Reactions

Abstract

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

Frontiers in pruritus research: scratching the brain for more effective itch therapy

“…Here induction of itch by histamine application coactivates the anterior cingulate and insular cortex, premotor and supplementary motor areas, cerebellum, primary somatosensory cortex, and thalamus (40)(41)(42). As done earlier for pain sensation, particular aspects of the itch sensation have been correlated with the activation of certain brain areas: spatial and temporal aspects may be processed in the primary somatosensory cortex, planning of the scratch response in the premotor and supplementary motor cortices, and affective and motivational aspects in the anterior cingulate (38,43) and insular cortex ( Figure 2). All these brain areas are also involved in pain processing (44).…”

Neuroimaging of Itch as a Tool of Assessment of Chronic Itch and Its Management

“…Positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG) have been commonly used during itch episodes to objectively document pruritus (Hsieh et al 1994;Darsow et al 2000;Drzezga et al 2001;Mochizuki et al 2003Mochizuki et al , 2007Mochizuki et al , 2009Herde et al 2007; Leknes et al 2007;Papoiu et al 2012). The majority of the studies focused on healthy subjects.…”

Pathogenesis and Treatment of Pruritus

“…There, the two sensations are projected by undetermined pathways to the cingulate and other cortical areas for final associative processing involving the parietal lobes, thus allowing perception of the unpleasant and distressing qualities of pain and itch. These areas recently have been further defined by functional positron emission tomography scan [11]. The prefrontal lobe determines the individual's itch and pain "thresholds."…”