Recently there have been a series of developments that now give a unique opportunity to investigate the mechanisms by which the nervous system becomes sensitized to pruritic stimuli. (1) The afferent sensory neurons involved in signaling itch have been documented, as well as (2) a population of spinal axons that likely transmit itch-related information to higher levels of the central nervous system. In addition, (3) an animal behavioral model for pruritus has been developed which (4) preliminary experiments have shown can be sensitized to itch-producing stimuli. Thus it will be possible to screen a variety of treatment protocols to determine which cause sensitization to pruritogens and to document the time course of sensitization. Sensitization will be quantified in terms of both response threshold and magnitude of response to a standard stimulus. Sensitization procedures will be emphasized that are relevant to the causes of chronic pruritus. It is proposed that after the time course of sensitization is established, experiments be done on anesthetized animals comparing the response of itch-related receptors inside and outside the zone of sensitization as well as compare the responses of itch-related pathways within the central nervous system. Parallel experiments will be conducted documenting the response of human subjects to pruritic stimuli and the alteration of response of normal human subjects to mildly sensitizing procedures. In summary, by comparing animal behavioral and human sensory responses with peripheral receptor and central pathway responses we are likely to gain valuable new insights into how the nervous system is altered by chronic pruritus.
