The role of the nervous system in rhinitis Seema Sarin, MD, Bradley Undem, PhD, Alvin Sanico, MD, Alkis Togias, MD  Journal of Allergy and Clinical Immunology  Volume 118, Issue 5, Pages 999-1014 (November 2006) DOI: 10.1016/j.jaci.2006.09.013 Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 1 Generation of nasal symptoms through neural pathways. Sensory nerves can be stimulated by products of allergic reactions and by external physical and chemical irritants. Signals are transmitted to the central nervous system (CNS), where they can trigger sensations (pruritus) and can further travel through secondary synapses to activate efferent motor (sneezing) and autonomic neurons. Action potentials traveling through parasympathetic efferent nerves can lead to glandular activation and rhinorrhea, as well as to some vasodilation. Suppression of sympathetic neural output, on the other hand, results in vasodilation and nasal congestion. Antidromic stimulation of sensory nerves with release of tachykinins and other neuropeptides at the nasal mucosa contributes to symptom development with glandular activation, vasodilation, and plasma extravasation. Neuropeptide release can also lead to leukocyte recruitment and activation. Collectively, events generated by the antidromic stimulation of sensory nerves constitute the phenomenon of “neurogenic inflammation.” Journal of Allergy and Clinical Immunology 2006 118, 999-1014DOI: (10.1016/j.jaci.2006.09.013) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 2 Pathways through which the nasal nervous system interacts with the immune system and with inflammatory processes. Discussion regarding each of these pathways can be found in various sections of the text. Journal of Allergy and Clinical Immunology 2006 118, 999-1014DOI: (10.1016/j.jaci.2006.09.013) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 3 Experimental methodology to assess the nasonasal secretory reflex using unilateral (single-nostril) neural stimulation with an 8-mm-diameter filter paper disc impregnated with a chemical stimulus (eg, histamine, bradykinin, and capsaicin) or its vehicle. The discs are preferably placed on the septal mucosa, but the lateral surface of the inferior turbinates can be used as well. The outcome is the amount of nasal secretion absorbed by preweighed, dry filter paper discs that are left on the nasal mucosa of both nostrils for 30 seconds and are reweighed after removal from the nose. The contralateral to the stimulus secretory response can be regarded as an index of reflex neural activity. Journal of Allergy and Clinical Immunology 2006 118, 999-1014DOI: (10.1016/j.jaci.2006.09.013) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 4 Comparison of subjects with perennial allergic rhinitis with healthy control subjects with respect to the secretory response obtained by means of multiple-dose (x-axis), single-nostril capsaicin challenge. The outcomes (y-axis) are the weights of secretions collected on filter paper discs that were applied on the ipsilateral and the contralateral to the challenge nostrils in the manner depicted in Fig 3. Individuals with rhinitis are 100-fold more sensitive than healthy control subjects. ED50 is defined as the dose of capsaicin causing 50% of the secretory response obtained with the highest dose; this was interpolated from the dose-response curve. P values reflect the ED50 comparisons of the 2 subject groups. Data used with permission from Sanico et al.88 Journal of Allergy and Clinical Immunology 2006 118, 999-1014DOI: (10.1016/j.jaci.2006.09.013) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions