Objectives　Regulation of pruritus is important to control the pathological condition in pruritic diseases, such as atopic dermatitis and urticaria. In this study, to evaluate the relationship between histamine and sensory nerves at skin level, we studied the effects of histamine on nerve growth factor（NGF）and substance P（SP）productions. Then, we tested the effects of the second-generation anti-histamines olopatadine and levocetirizine on their response.
Methods and Results　At first, in order to evaluate the anti-histamine effects of olopatadine and levocetirizine in skin, we investigated the effects on passive cutaneous anaphylaxis（PCA）and histamine-induced plasma leakage in rat skin. Olopatadine and levocetirizine significantly inhibited PCA reaction, but the inhibitory dose of olopatadine was lower than that of levocetirizine. Pretreatment with olopatadine 1 or 8 h before the challenge inhibited the low-dose and high-dose histamine-induced reactions to the same extent. But, the effect of levocetirizine against the reaction induced by high-dose histamine was weak compared to that against the reaction induced by low-dose histamine, and the inhibitory effects of pretreatment administered 8 h before the challenge was diminished, whereas the pretreatment administered 1 h before the challenge was effective. Next, the histamine-induced productions of NGF and SP were examined. The productions of NGF and SP in skin increased, with the peaks being observed at 8 h after the challenge；the increased productions were detected up to 24 h after the challenge. Olopatadine significantly inhibited the increases of NGF and SP production. On the other hand, levocetirizine did not show marked inhibitory effects.
Conclusions　Histamine induced the production of NGF and SP in rat skin. Both olopatadine and levocetirizine inhibited PCA reaction and histamine-induced plasma leakage. The effect of olopatadine exceeded and persisted longer than that of levocetirizine. Olopatadine inhibited the production of NGF and SP induced by histamine. These results suggest the possibility that histamine is involved in pruritus directly and via induction of SP and NGF. These results also suggested that the inhibitory effects of olopatadine on the histamine-induced NGF and SP productions might be concerned to exert additional biological effects besides its blockade of the histamine H₁ receptor.