Noninvasive system for evaluating allergen-induced nasal hypersensitivity in murine allergic rhinitis

Abstract

Until now there has been no method for physiologically evaluating nasal hypersensitivity in mice. Enhanced pause (Penh) has been used as an indicator that reflects changes in the lower airway. Recently, however, there is disagreement regarding the significance of the Penh system; this is because Penh is not essentially a physiological parameter, and it might not necessarily represent a change in the lower respiratory tract. The purpose of the present study is to investigate whether Penh could be applicable for analyzing nasal hypersensitivity in mice. BALB/c mice were sensitized with ovalbumin (OVA) through a combination of intraperitoneal injection and daily intranasal challenge in an awake condition. Penh was measured at each time point during sensitization, or a serial change in Penh value was followed after the final nasal challenge and the effect of treatment was assessed. Following sensitization and nasal challenge, the Penh value gradually increased and showed a significant difference on day 14. Changes in IgE, eosinophil infiltration into nasal mucosa, and OVA-induced symptoms all strongly correlated with the increase in Penh. On day 19, after OVA nasal provocation, Penh gradually increased and reached maximal values 25 min after the challenge. Pretreatment with dexamethasone or a histamine H1 blocker significantly suppressed this increase in Penh. We confirmed that intranasal OVA challenge did not induce bronchoconstriction by measuring airway resistance and bronchoalveolar lavage fluid, and through histological examination. These results clearly demonstrate that Penh could be a useful noninvasive indicator for studying nasal hypersensitivity.

Pharmacology of AM211, a Potent and Selective Prostaglandin D2Receptor Type 2 Antagonist That Is Active in Animal Models of Allergic Inflammation

“…The procedures for inducing allergic rhinitis symptoms were adapted from those detailed in Nakaya et al (2006). In brief, mice were immunized by an intraperitoneal injection of 10 g of OVA complexed with Imject Alum in a volume of 0.2 ml on days 1 and 8.…”

Intranasal Administration of Semaphorin-3A Alleviates Sneezing and Nasal Rubbing in a Murine Model of Allergic Rhinitis

“…AR model mice were established based on the previously described methods (26,27), with minor modifications. The experimental timetable is provided in Fig.…”

From Mouse to Man: Translational Value of Animal Models of Allergic Rhinitis

“…These features are likely overlooked with routine examination of hemotoxylin and eosin-stained tissue, and can be underestimated if mucus detection relies on only a single stain, rather than both periodic acid-Schiff (PAS) and alcian blue, which stain for neutral and acidic mucosubstances, respectively. Mucosal and airway recruitment of eosinophils, neutrophils, and mast cells are commonly reported in both experimental and clinical AR (Miyahara et al 2006;Nakaya et al 2006;Wagner et al 2002;Wagner et al 2008). Furthermore, eosinophils in nasal biopsies or in nasal lavage fluid are highly correlated with most symptoms in AR patients (Ciprandi et al 2004a;2004b).…”

“…Some studies have taken advantage of WBP in rhinitis models where intranasal challenge protocols are designed for allergen delivery to be limited to the nose, and not to reach the deep lung. For example, Nakaya and coworkers measured increases in Penh after intranasal histamine or allergen challenge in allergic BALB/c mice (Nakaya et al 2006). Although modest pulmonary inflammation was detected, there were no allergen-induced changes in lower airway resistance when analyzed by separate, invasive techniques that bypassed the nose.…”