Itch accompanies many neurological, dermatological and systemic diseases and leads to suffering and loss in the quality of life. The peripheral neuronal mechanisms underlying this sensation in human are still poorly understood. The overall goal of our proposal is to determine how acute itch and the prolonged itch from a pruritic disease are encoded in the discharges of cutaneous nociceptors. We propose electrophysiological experiments in nonhuman primate to characterize the responses to pruritic chemical stimuli in subtypes of peripheral nociceptive nerve fibers and complementary, correlative psychophysical studies in human to determine the role of these different neuronal populations in itch sensation. We will test the predictions of models that propose that cutaneous nociceptors differentially signal pruritic and algesic stimuli either by the overall number of afferents activated or by the rates or patterns of their discharges. In a clinically relevant model of prolonged itch, namely the SADBE model of allergic contact dermatitis, we will investigate the neuronal mechanisms of spontaneous itch and enhanced itch to chemical and heat stimuli using psychophysical studies in humans and electrophysiological recordings from nociceptive afferents in monkeys. By studying both acute and prolonged itch, we will be able to identify, for the first time, changes that occur in the peripheral nervous system in a clinically relevant itch condition. A better understanding of how nociceptors mediate the sensation of itch in normal and pruritic skin will increase the possibility of developing and evaluating novel, peripherally acting drugs that reduce the abnormal nociceptor function underlying chronic itch.
Although itch is a significant clinical problem affecting millions of people worldwide, the neuronal mechanisms of this sensation in human are not well understood. Using a combination of psychophysical studies in human and electrophysiological studies in non-human primate, we will investigate how itch is encoded in the neuronal activity of different types of peripheral nerve fibers in normal skin and in inflamed and itchy skin produced by allergic contact dermatitis. The outcomes will lead to a better understanding of how acute itch in normal skin and prolonged itch from a clinically relevant pruritic disorder are encoded by nerve fibers and thereby provide potential neuronal targets for future development of peripherally acting anti-pruritic drugs.
