THE PRURITOGENIC AND INFLAMMATORY EFFECTS OF PROSTANOIDS IN THE CONJUNCTIVA

The therapeutic utility of cyclooxygenase (GO) inhibitors, such as ket orolac, in reducing the inflammatory events associated with allergic c onjunctivitis is not unexpected since prostanoids (PC) elicit conjunct ival redness (PGD(2), PGE(2), PGF(2 alpha)), edema (PGD(2), TxA(2)), e osinophil infiltration (PGD(2), PGJ(2)) and mucous cell discharge (PGD (2), PGJ(2), TxA(2)). Recently, topically administered ketorolac has a lso been reported to alleviate the itching associated with allergic co njunctivitis. This was viewed as intriguing since CO inhibitors are no t regarded as useful for treating itching dermatoses and PGs do not el icit itching when applied to the skin. In order to investigate the ant ipruritic activity of ketorolac, we developed a model for reproducibly measuring ocular surface itch responses. The model involves itch-scra tch responses to pruritogens applied locally to the ocular surface. Pa inful and foreign body stimuli do not produce an itch-scratch response . Unlike reported skin studies, PGE(2) was a potent itch-producing sub stances in the conjunctiva. PGD(2) was weakly pruritogenic but PGF(2 a lpha) and the TxA(2)-mimetic U-46619 were inactive. The PG precursor a rachidonic acid was also a potent pruritogen and its effects were inhi bited by ketorolac pretreatment. Ketorolac also dose-dependently inhib ited the itching associated with experimental allergic conjunctivitis. It appears that PGs are potent itch-producing substances in the conju nctiva and the anti-itch efficacy of ketorolac in allergic conjunctivi tis appears to involve inhibition of conjunctival PG biosynthesis from arachidonic acid.