QUANTITATIVELY CONTROLLED EXPERIMENTAL PRURITUS

AT PRESENT, NO DRUGS HAVE BEEN DEVELOPED THAT ACT DIRECTLY TO SUPPRESS THE SENSATION OF ITCHING BY INHIBITING THE RESPONSE OF THE ITCH-SIGNALING RECEPTORS THAT INNERVATE THE SKIN, IN SPITE OF THE FACT THAT THERE IS A POTENTIALLY LARGE MARKET FOR SUCH PRODUCTS. UNLIKE PAIN RESEARCH WHERE THERE ARE WELL-DEVELOPED HUMAN MODELS FOR THE ASSESSMENT OF PAIN INHIBITION, QUANTITATIVE MEASURES OF THE INTENSITY OF ACUTE PRURITUS HAVE BEEN LACKING. PRELIMINARY EXPERIMENTS HAVE DEMONSTRATED THE FEASIBILITY OF INDUCING EXPERIMENTAL PRURITUS IN HUMAN SUBJECTS IN A QUANTITATIVE MANNER THAT HAS ADVANTAGES OVER PREVIOUS TECHNIQUES AND OF CONTINUOUSLY MONITORING THE SUBJECT'S ESTIMATE OF THE MAGNITUDE OF PRURITUS. THIS TECHNIQUE NOT ONLY CAN BE USED TO ADMINISTER A CLASSICAL PRURITOGEN INTO THE SUPERFICIAL LAYERS OF SKIN IN A CONTROLLED MANNER, BUT ALSO TO INDUCE MAST CELL DEGRANULATION. THIS PROJECT WILL REFINE THIS MODEL BY USING CONTROL AND DOSE-RESPONSE EXPERIMENTS IN A MATCH-PAIRED STIMULUS PARADIGM AND BY INVESTIGATING AND REDUCING SUBJECT-TO-SUBJECT, AS WELL AS INTRASUBJECT, VARIABILITY. THESE METHODS WILL THEN BE USED TO SCREEN HERBAL PREPARATIONS WITH PROMISING ANTIPRURITIC PROPERTIES. BECAUSE THE EXTRACTION OF ACTIVE MOLECULES IS BOTH EXPENSIVEAND TIME CONSUMING, IT IS NECESSARY TO OBTAIN HARD EVIDENCE AS TO WHICH HERBS ARE MOST PROMISING BEFORE EMBARKING ON THE EXTRACTION PROCESS. THE EXPERIMENTS PLANNED ARE A VITAL LINK IN THIS EVALUATION PROCESS.