1. ¹Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
2. ²Department of Dermatology and Allergy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
3. ³Division of Environmental Dermatology and Allergy GSF/TUM, ZAUM-Center for Allergy and Environment, Technische Universität München, Munich, Germany
4. ⁴Department of Neuroradiology, Institut für Röntgendiagnostik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

Correspondence: Dr Michael Valet, Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Strasse 22, München 81675, Germany. E-mail: valet@lrz.tum.de

⁵These authors contributed equally to this work

Received 12 February 2007; Revised 30 May 2007; Accepted 31 May 2007; Published online 26 July 2007.

Abstract

Human neuroimaging studies on the physiology of itch have been hampered by the lack of reproducible "on–off" stimuli. Using a previously established biphasic temperature stimulus model, we investigated the cerebral activation pattern of itch processing in 12 healthy volunteers with functional magnetic resonance imaging. Itch was provoked on the right forearm with skin prick application of 1% histamine-dihydrochloride. Local temperature modulation allowed reproducible itch provocation above scratch threshold (defined as 33/100 on a visual analogue scale) during 25°C, whereas itch declined below scratch threshold during the 32°C stimulation period. No itch sensation was reported using 0.9% saline with temperature modulation. Itch sensation above scratch threshold was associated with increased activation of the thalamus, presupplementary motor area, anterior insular, inferior parietal, and dorsolateral prefrontal cortex, and decreased activation of the orbitofrontal, medial frontal, mid-cingulate, and primary motor cortex in comparison to saline. The biphasic temperature model allows rapid modulation of histamine-induced itch. The evoked itch sensation above scratch threshold is processed by a network of brain regions contributing to the encoding of sensory, emotional, attention-dependent, cognitive-evaluative and motivational aspects of itch.