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 Ca(2+) 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.