In OVA-sensitized rats, the number of sneezing episodes increases and the nasal skin temperature rises were provoked after OVA challenge. Olopatadine reduced the increased frequency of sneezing and the nasal temperature rise. The levels of NGF and VEGF in NALF also were increased by OVA challenge. Olopatadine inhibited the increased NGF and VEGF production.
The efficacy of antihistamines on rhinitis was compared by measuring nasal symptoms and rhinomanometry, which olopatadine is considered effective for symptoms such as sneezing, rhinorrhea and nasal obstruction [3
]. In clinical study, the antihistaminic activity of levocetirizine and fexofenadine was assessed using facial thermography during nasal provocation tests with histamine and allergen [6
]. In this study, olopatadine reduced the sneezing and the risen nasal temperature in the OVA-induced allergic rhinitis model. Therefore the assay using thermography also could become a useful clinical indicator in animal model.
In this study, skin minimum temperature of the nose area did not changed, but skin maximum and mean temperature rise were observed during 0.25-3 h, and those rises were observed again at 6 h after OVA challenge. The main symptoms of AR are observed in the early phase and the late phase of the disease. The early phase response, characterized by sneezing, rhinorrhea and nasal congestion, occurs within a few minutes of antigen exposure and subsides after 30-90 min. In contrast, the late phase reaction, characterized mainly by nasal congestion, begins around 4-8 h after the early phase response [20
]. Olopatadine significantly inhibited the decrease in the nasal cavity volume at the early phase and the late phase after the antigen challenge [21
Nasal congestion may be due to the increased nasal blood flow and nasal temperature increase may be involved in blood flow; blood flow is thought to cause the swelling of nasal mucosa. The swelling of nasal mucosa by antigen are considered a direct effect on the nasal mucosa vasculature of chemical mediators such as histamine, cysteinyl leukotrienes and PAF [22
]. It is also reported that capsaicin sensitive sensory nerve reflexes were related to nasal blockage [25
]. It has been shown that olopatadine inhibits the release and the action of histamine, the release of peptide leukotrienes [26
], the production of PAF and leukotriene B4
, and the release of neuropeptides [27
]. Accordingly, the efficacy of olopatadine on nasal temperature increase is likely to be based on these actions; that is, inhibitory actions on the release of histamine, peptide leukotrienes and neuropeptides, and on the production of PAF as well as based on the antagonistic actions on histamine.
VEGF is produced from mast cell and is involved in type I allergy [28
]. Therefore, VEGF is thought to contribute to the swelling of nasal mucosa by the increased vascular permeability in the early phase of AR. It is suggested that olopatadine is suppressing the swelling of nasal mucosa by the inhibitory effect of LTs [21
]. Relationship between blood flow, swelling of nasal mucosa and nasal temperature in this model is not clear. The inhibitory effect on nasal temperature of olopatadine was suggested that it is involved H1
antagonistic effects and the inhibition of LTs release in addition to the inhibition of increased histamine and VEGF.
NGF increases the sensitivity to sneeze reflex and makes an increase in nasal rhinorrhea and plasma leakage by sensory nerve stimulation [29
]. The amount of NGF in NALF of patients with AR is increasing compared to healthy volunteers, it were additional increased by the antigenic exposure [30
]. Neuropeptides positive nerve fibers are increased in nasal mucosa of patients with AR. Neuropeptides may exacerbate further exposure to antigen reaction by encouraging the extension of nerve fibers. In this study, olopatadine inhibited the NGF production. These results suggest that the suppression of the increase in NGF might partially be involved in the improvement of allergy-like behavior and nasal temperature increase.
Olopatadine reduced the risen nasal temperature in the OVA-induced allergic rhinitis model. Therefore the assay using thermography could become a useful clinical indicator in animal model. More detailed studies will be required to ascertain the precise mechanism of action of olopatadine on nasal blockage. These results suggest that the suppression of the increased NGF and VEGF levels might partially be involved in the improvement of allergy-like behavior (sneezing and nasal skin temperature rise) by the treatment of olopatadine.