Investigation of capsaicin-induced superficial punctate keratopathy model due to reduced tear secretion in rats.

PURPOSE: The present study investigated the usefulness of the superficial punctate keratopathy (SPK) model due to reduced tear secretion induced by the injection of capsaicin in neonatal rats. METHODS: On postnatal day 4, rats were injected subcutaneously with a single dose of capsaicin. Ocular surface symptoms were evaluated by measuring corneal sensitivity, tear secretion and corneal fluorescein score. Furthermore, the effect of pilocarpine was investigated by measuring tear secretion and corneal fluorescein score in this model. The influence of discontinuation of pilocarpine application was also examined. RESULTS: Capsaicin caused a dose-dependent reduction of tear secretion and increase of corneal fluorescein score. In addition, 50 mg/kg capsaicin-treated rats showed a sustained decrease of corneal sensitivity and tear secretion, and an increase of corneal fluorescein score compared with vehicle-treated rats. Moreover, capsaicin-treated rats showed SPK. Instillation of pilocarpine significantly increased tear secretion and tended to improve the corneal fluorescein score by repeated application, whereas tear secretion and corneal fluorescein score in the pilocarpine-treated rats returned to the same level as that of capsaicin-treated rats after discontinuation of pilocarpine application. CONCLUSIONS: Injection of capsaicin in rats induced stable SPK due to reduced tear secretion accompanied by a decrease of corneal sensitivity. Thus, it may be concluded that this model is essentially similar to SPK due to reduced tear secretion and could be used in the development of appropriate new drugs for therapy.

Synergetic effects of prednisolone and olopatadine on atopic dermatitis model of hairless mice.

We investigated the synergetic effects of glucocorticoid and histamine H1 receptor antagonists on an atopic dermatitis model. Hairless mice were used in this study and an atopic dermatitis model was made by repeated application of 2,4,6-trinitrochlorobenzene. The effects of glucocorticoid, histamine H1 receptor antagonists, and the simultaneous use of these drugs were investigated by measuring scratching behavior, skin symptoms and nerve growth factor (NGF) in the skin. Topical application of prednisolone significantly inhibited scratching behavior, skin symptoms and NGF contents in the skin by repeated application. Olopatadine also showed a significant effect on scratching behavior and NGF contents in the skin, whereas chlorpheniramine showed no significant inhibitory effect on these indices. Furthermore, the combined use of prednisolone and olopatadine potentiated the inhibition of scratching behavior, skin symptoms, and NGF in the skin. From these findings, olopatadine potentiated the inhibitory effect of prednisolone on the symptoms of atopic dermatitis by inhibiting NGF.

Effect of topical application of Brazilian propolis on scratching behavior induced by compound 48/80 in mice.

BACKGROUND AND AIM: We investigated the effect of topical application of Brazilian propolis on scratching behavior induced by compound 48/80 in mice. RESULTS: Propolis inhibited compound 48/80-induced scratching behavior when applied immediately after treatment with propolis at a dose of 3 mg/site. Dibucaine 0.3 mg/site also significantly inhibited compound 48/80-induced scratching behavior immediately after application. On the other hand, propolis inhibited compound 48/80-induced scratching behavior even 15, 30 and 60 min after application; however, dibucaine showed no significant inhibition of compound 48/80-induced scratching behavior 15, 30 and 60 min after application. In addition, propolis had no effect on increased vascular permeability just after application, but the drug had a significant effect 15, 30 and 60 min after application. On the contrary, histamine-induced scratching behavior was inhibited significantly by propolis just after application. On the other hand, propolis significantly inhibited histamine release from rat mast cells induced by compound 48/80 at a concentration of more than 10 microg/ml. CONCLUSION: From these results, it can be concluded that inhibition of scratching behavior induced by topical application occurred by both its local anesthetic and systemic action through inhibition of histamine release.

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on scratching behavior in mice.

The present study was performed to study the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on scratching behavior in hairless mice, which are highly sensitive to pruritogens (mediators causing itching), except for histamine, and are suitable for time-course studies due to their hairless skin. TCDD is a well-known environmental pollutant that causes skin diseases with itching; therefore, we examined whether TCDD induced itching. Oral administration of TCDD caused no increase in scratching behavior when used alone, whereas TCDD in combination with distilled water or acetone/olive oil application caused a significant increase in scratching behavior. Furthermore, nerve growth factor (NGF) content in the skin increased significantly. A single administration of chlorpheniramine (histamine H1 receptor antagonist), tranilast (chemical mediator release inhibitor) and olopatadine (histamine H1 receptor antagonist) had no effect on scratching behavior induced by TCDD in combination with acetone/olive oil application. With repeated administration for 7 days, chlorpheniramine and tranilast had no effect on scratching behavior, whereas olopatadine significantly inhibited scratching behavior. In addition, only olopatadine significantly inhibited NGF content in the skin. From these findings, it can be concluded that TCDD is not a pruritogen but causes alloknesis (itchy skin) with the simultaneous use of trivial external stimulation. In addition, it was found that drugs which decreased skin NGF contents may inhibit this scratching behavior.

Effect of Brazilian propolis on sneezing and nasal rubbing in experimental allergic rhinitis of mice.

We studied the effect of Brazilian propolis on sneezing and nasal rubbing in experimental allergic rhinitis of mice. A single administration of propolis caused no significant effect on both antigen-induced nasal rubbing and sneezing at a dose of 1000 mg/kg, but a significant inhibition was observed after repeated administration for 2 weeks at this dose. Propolis caused no significant inhibitory effect on the production of total IgE level after repeated administration of 1000 mg/kg. The drug also caused no significant inhibition of histamine-induced nasal rubbing and sneezing at a dose of 1000 mg/kg. On the other hand, propolis significantly inhibited histamine release from rat mast cells induced by antigen and compound 48/80 at a concentration of more than 10 microg/ml. These results clearly demonstrated that propolis may be effective in the relief of symptoms of allergic rhinitis through inhibition of histamine release.

Effect of histamine H4 receptor antagonist on allergic rhinitis in mice.

The aim of this study was to clarify the effect of histamine H(4) receptor antagonist, JNJ7777120 (1-[(5-Chloro-1H-indol-2-yl)carbonyl]-4-methyl-piperazine) on allergic rhinitis in mice. We measured allergic symptoms (sneezing and nasal rubbing), serum total IgE and the levels of cytokines in nasal lavage fluid. Histamine H(4) receptor antagonist, JNJ7777120, caused the dose-dependent inhibition of nasal symptoms by single and repeated intranasal administrations; however, JNJ7777120 caused no inhibition of serum total IgE by single and repeated intranasal administrations. Therefore, we investigated the effect of JNJ7777120 by oral administration. JNJ7777120 also caused a significant inhibition of nasal symptoms by both single and repeated oral administrations. In addition, repeated oral administration of JNJ7777120 caused significant inhibition of serum total IgE. Furthermore, JNJ7777120 caused a significant decrease in the levels of IL-4 and a significant increase in the levels of IFN-gamma in nasal lavage fluid. These results indicated that histamine H(4) receptor is closely related with allergic rhinitis and is important in the pathogenesis of allergic rhinitis. From these results, it can be concluded that histamine H(4) receptor antagonist might be a new strategy to treat allergic rhinitis with immunomodulatory function.

Role of histamine H(4) receptor in allergic conjunctivitis in mice.

We investigated the character of histamine H(1) receptor and H(4) receptor in allergic conjunctivitis. Histamine is the most important mediator in allergic conjunctivitis. We measured eye scratching behavior and allergic-like symptoms score, that is, hyperemia and edema in ICR mice, and examined which receptors intimately involved in allergic conjunctivitis. Histamine caused a dose-dependent eye scratching behavior and allergic-like symptoms. Histamine H(1) receptor antagonist (levocabastine) and H(4) receptor antagonist (JNJ7777120) inhibited eye scratching behavior and histamine H(1) receptor antagonist inhibited allergic-like symptoms induced by histamine. Additionally, combination of levocabastine and JNJ7777120 caused more potent inhibition in allergic conjunctivitis. On the other hand, both selective histamine H(1) receptor agonist (HTMT) and selective H(4) receptor agonist (4-methylhistamine) induced a dose-dependent eye scratching behavior and allergic-like symptoms. JNJ7777120 inhibited the effect of HTMT. However, levocabastine caused no inhibition on the response of 4-methylhistamine. H(4) receptor was closely related with allergic conjunctivitis. H(4) receptor antagonists may be effective in allergic conjunctivitis which showed no inhibition by histamine H(1) receptor antagonists.