Figure 18: Mucosal irritation and neurogenic inflammation
An irritant binds to a vanilloid type I receptor (VR1) on a trigeminal, non-myelinated group C fiber within the airway mucosa (nociceptor). Local influx of sodium and calcium ions results in circumscribed membrane depolarization, which in turn opens voltage gated sodium channels (VGSC) and generates an action potential along the nerve fiber. This action potential runs orthodromically (in the correct direction) toward the Gasserian ganglion, where transmitter substances including glutamate, Substance P (SP) und Calcitonin Gene Related Peptide (CGRP) transfers the signal to central neurons responsible for the perception of irritation and pain. The action potential also runs antidromically toward the periphery, where tachykinins such as SP, CGRP and Neurokinin A (NKA) are released. They activate the Neurokinin 1 (NK1) receptor on glandular cells, respiratory epithelium and endothelium of neighbouring vessels. Thus they mediate hypersecretion, vasodilation and inflammatory cell infiltration.