CHARACTERIZATION OF A BEHAVIORAL-MODEL FOR PERIPHERALLY EVOKED ITCH SUGGESTS PLATELET-ACTIVATING-FACTOR AS A POTENT PRURITOGEN

The studies described herein characterize animal behavioral models for conjunctival and cutaneous itch. Histamine was used as the reference stimulus for model development because it is firmly established as a p ruritogen in both conjunctiva and skin. Itching evokes the desire to s cratch in human subjects, so hind limb scratching at the afflicted are a was used to identify pruritogenic stimuli. Under optimized environme ntal conditions, hind limb scratching behavior yielded substantial and highly reproducible responses. The conjunctival itch-scratch response was delineated from pain and foreign body sensations by using appropr iate stimuli. Examination of a large and diverse variety of autocoids revealed that only histamine, platelet-activating factor (PAF) and ara chidonic acid and its cyclooxygenase metabolite prostaglandin E(2) pos sessed meaningful pruritogenic activity. PAF-induced ocular pruritus d id not involve histamine release, according to studies with appropriat e antagonists. Thus PAF-induced ocular pruritus was unaffected by the histamine H-1-receptor antagonist pyrilamine but was substantially att enuated by the PAF antagonists WEB 2086 and CV-6209 and was virtually abolished by E-6123. Similar itch-scratch behaviors were quantified in hairless guinea pig skin following the application of cowhage or the iontophoretic administration of histamine and PAF. Findings from these newly developed itching models suggest that PAF could be an important mediator of the pruritic sensation by activating a population of nerv e endings responsible for encoding the itch sensation.