The general objective of this research is to initiate quantitative study of the sensation of itch and to elucidate the neurophysiological basis of this sensation. Specific objectives are to (1) develop an instrument for reproducible chemical excitation of itch endings (""""""""pruritometer""""""""); (2) use the pruritometer to study human itch sensation; (3) develop an animal model for investigation of pruritus neurophysiology; (4) study primary afferent receptors and itch projection pathways using the animal model; (5) investigate in humans the pathophysiological mechanisms responsible for itch. The pruritometer is based upon a special perfusion chamber, computer controlled protocols for chemical stimulation, and removal of the stratum corneum to expose itch afferent endings. Chemical agents will include histamine, trypsin, kallikrein, substance P, and potential itch inhibitors such as H-1 and H-2 histamine antagonists and histamine depleting agents. The human psychophysics experiments will measure stimulus/dose-response relations, investigate itch submodalities and temporal characteristics (detection, aversion, adaptation, habituation), interaction of itch with other modalities (pain and thermal), and interaction of itch agonists and antagonists. A decerebrate animal will be used for the animal model, with the pruritometer applied as in human studies. Activity of rear leg muscles will be monitored via isometric force transducers and emg recording, and the contraction pattern characteristic of """"""""scratch"""""""" will be used as measure of itch sensation. Using the animal model with chemical and electrical stimulation, properties of primary afferent fibers will be described and itch projection pathways in the CNS traced. In the human clinical studies, the pruritic response associated with pathophysiological conditions (e.g., atopic dermatitis) will be characterized--e.g., do such patients have lower thresholds to pruritogens, is the time course of sensory response different from normal, etc.--and the effectiveness of proposed therapeutic agents will be evaluated. By investigating the basic neurophysiology and psychophysics of itch, and by extending the investigation to disease states, this research may provide a rational basis for treatment of accursed itch.
