1. ¹Department of Dermatology, IZKF Münster, Ludwig Boltzmann-Institute for Immunobiology of the Skin, University Hospital Muenster, Muenster, Germany
2. ²Department of Pathology and Molecular Medicine, The Brain-Body Institute, McMaster University, St Joseph's Healthcare Hamilton, Ontario, Canada
3. ³Department of Anesthesiology and Critical Care Medicine, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Mannheim, Germany
4. ⁴Department of Dermatology and Allergy, Charité University of Berlin, Berlin, Germany
5. ⁵School of Public Health, University of California, Berkeley, California, USA
6. ⁶Department of Physiology, Medical and Health Science Center, Research Center for Molecular Medicine, University of Debrecen, Debrecen, Hungary

Correspondence: Dr Martin Steinhoff, Department of Dermatology, IZKF Münster, Ludwig Boltzmann-Institute for Immunobiology of the Skin, University Hospital Münster, Von-Esmarch-Strae 58, Münster D-48149, Germany. E-mail: msteinho@uni-muenster.de

Received 19 July 2005; Revised 30 December 2005; Accepted 6 January 2006.

Abstract

Pruritus (itch) can be defined as an unpleasant cutaneous sensation associated with the immediate desire to scratch. Recent findings have identified potential classes of endogenous "itch mediators" and establish a modern concept for the pathophysiology of pruritus. First, there in no universal peripheral itch mediator, but disease-specific sets of involved mediators. Second, numerous mediators of skin cells can activate and sensitize pruritic nerve endings, and even modulate their growth. Our knowledge of itch processing in the spinal cord and the involved centers in the central nervous system is rapidly growing. This review summarizes the current information about the significance of neuron–skin interactions, ion channels, neuropeptides, proteases, cannabinoids, opioids, kinins, cytokines, biogenic amines, neurotransmitters, and their receptors in the pathobiology of pruritus. A deeper understanding of these circuits is required for the development of novel antipruritic strategies.