Itch Induced by a Novel Method Leads to Limbic Deactivations— A Functional MRI Study

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Abstract
Functional brain imaging studies on itch usually use histamine as a stimulus and, in consequence, have to cope with the highly variable time course of this particular itch sensation. In this study, we describe a novel method of histamine application. To provoke itch, a mixture of histamine and codeine was applied through intradermally positioned microdialysis fiber. The itch was terminated by lidocaine application through the same fiber. During one fMRI session, this procedure was repeated four times in four different microdialysis fibers, including one placebo control. Itch ratings of the subjects were correlated with blood-oxygen-level-dependent (BOLD) effects. In a subsequent experiment performed in the same fMRI session, heat pain was provoked in the right forearm with a Peltier thermode. During both experiments, activation clusters were found in brain areas that have been described previously to be frequently activated in response to painful stimuli. This includes prefrontal areas, supplementary motor areas (SMA), premotor cortex, anterior insula, anterior midcingulate cortex, S1, S2, thalamus, basal ganglia, and cerebellum. In general, itch stimulation entailed more activation clusters, in particular on the contralateral brain side. Only on itch, but not on heat pain, negative BOLD signals were found in the subgenual anterior cingulate cortex and the amygdala. The latter results may be associated with the itch induced urge to scratch. Amygdala deactivation may be related to the preparation of scratching by aiming to dissolve the otherwise aversive effects of the noxious scratch stimuli. These negative BOLD effects may also be attributed to the stressful character of itch stimulation.