Neural Abnormalities in Nonallergic Rhinitis

Sensory nerve endings within the airway epithelial cells and the solitary chemoreceptor cells, synapsing with sensory nerves, respond to airborne irritants. Transient receptor potential (TRP) channels (A1 and V1 subtypes, specifically) on these nerve endings initiate local antidromic reflexes resulting in the release of neuropeptides such as substance P and calcitonin G-related peptides. These neuropeptides dilate epithelial submucosal blood vessels and may therefore increase transudation across these vessels resulting in submucosal edema, congestion, and rhinitis. Altered expression or activity of these TRP channels can therefore influence responsiveness to irritants. Besides these pathogenic mechanisms, additional mechanisms such as dysautonomia resulting in diminished sympathetic activity and comparative parasympathetic overactivity have also been suggested as a probable mechanism. Therapeutic effectiveness for this condition has been demonstrated through desensitization of TRPV1 channels with typical agonists such as capsaicin. Other agents effective in treating nonallergic rhinitis (NAR) such as azelastine have been demonstrated to exhibit TRPV1 channel activity through the modulation of Ca2+ signaling on sensory neurons and in nasal epithelial cells. Roles of antimuscarinic agents such as tiotropium in NAR have been suggested by associations of muscarinic cholinergic receptors with TRPV1. The associations between these channels have also been suggested as mechanisms of airway hyperreactivity in asthma. The concept of the united airway disease hypothesis suggests a significant association between rhinitis and asthma. This concept is supported by the development of late-onset asthma in about 10–40 % of NAR patients who also exhibit a greater severity in their asthma. The factors and mechanisms associating NAR with nonallergic asthma are currently unknown. Nonetheless, free immunoglobulin light chains and microRNA alteration as mediators of these inflammatory conditions may play key roles in this association.