H3 Receptor Expression in the Spinal Trigeminal Nucleus Caudalis in a Rat Model of Allergic Rhinitis

Background: Allergic rhinitis is one of the most frequently observed allergic diseases. Although antihistamine medication is an effective symptomatic treatment for this disease, it is not suffcient enough to improve quality of life, requiring an additional treatment. Excessive sneezing is a typical symptom of allergic rhinitis in response to immunological release of histamine, and we hypothesized that this could be due to characteristic changes on the reflex pathway, particularly a nucleus receiving nasal trigeminal afferents, the spinal trigeminal nucleus caudalis (Sp5C), via a histamine mechanism(s). In the present study, we created an allergic rhinitis model by conventional methods, harvesting brainstem tissues to perform immunohistochemistry for histamine receptor subtype 3 (H3R) in Sp5C. Methods: Male Fisher 344 rats (8 weeks old) were sensitized and nasally challenged to Ovalbumin. After the Ovalbumin challenge into the nasal cavity, the number of sneezing was visually counted for 13 min and repeated for 7 days. After that, animals were euthanized, brainstems were extracted, and immunohistochemistry were performed with various antibodies, including anti-H3R and -GFAP. In some animals, to identify the subregion within Sp5C where nasal trigeminal afferents are transmitted from the nasal mucosa, capsaicin (0.3mM), a potent nociceptive substance, was administered into the nasal cavity and then immunohistochemistry of c-Fos expression was performed. Quantitative analysis was performed by area of fluorescent staining. Results: Intranasal administration of capsaicin markedly increased c-Fos expression in Sp5C compared to non-administration control, confirming the subregion of Sp5C receiving nasal afferent information. The allergic rhinitis model rats showed a significant increase in sneezing frequency in response to Ovalbumin nasal challenge compared to non-sensitized rats challenged with Ovalbumin or saline (56.8±3.9 vs. 16.6±1.6 vs. 23.7±3.2 [sneezes during a total observation period]; p<0.001). The expression pattern of H3Rs was punctate and co-stained with GFAP in many cases. Both H3 receptor and GFAP expressions were significantly decreased in allergic model rats compared to control rats (control vs. allergic; 21.2±1.2 vs.6.4±0.5 [%] in H3Rs, p<0.001; 16.2±0.5 vs.10.9±0.8 [%] in GFAP, p<0.001). No difference in DAPI staining was observed (14.5±0.8 vs.13.7±0.5 [%], p=0.223), suggesting similar population of cells in data analyzed from both groups. Discussion: These results may suggest that Sp5C is part of the sneezing reflex pathway and that a decrease in H3Rs, including those on astrocytes, is involved in worsening clinical symptoms of allergic rhinitis such as excessive sneezing. This research was supported by KAKENHI, Grant-in-Aid for challenging Exploratory Research # 21K19182. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.