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 pruritogen in both conjunctiva and skin. Itching evokes the desire to scratch in human subjects, so hind limb scratching at the afflicted area was used to identify pruritogenic stimuli. Under optimized environmental 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 appropriate stimuli. Examination of a large and diverse variety of autocoids revealed that only histamine, platelet-activating factor (PAF) and arachidonic acid and its cyclooxygenase metabolite prostaglandin E2 possessed meaningful pruritogenic activity. PAF-induced ocular pruritus did not involve histamine release, according to studies with appropriate antagonists. Thus PAF-induced ocular pruritus was unaffected by the histamine H1-receptor antagonist pyrilamine but was substantially attenuated 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 nerve endings responsible for encoding the itch sensation.
Woodward
D F
DF
Department of Biological Sciences, Allergan, Inc., Irvine, California.
Nieves
A L
AL
Spada
C S
CS
Williams
L S
LS
Tuckett
R P
RP
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008297:Male; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000494:pharmacology*; D011537:Pruritus / Q000139:chemically induced*; D011726:Pyridinium Compounds / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; D014230:Triazoles; C053321:CV 6209; C052518:WEB 2086; D006632:Histamine