Release of
neuropeptides from sensory nerves causes an increase in vascular permeability, plasma extravasation and
edema. The sensory nerves in the airways can be activated by electrical stimulation of the vagus nerve or by application of chemical and mechanical irritants, such as
capsaicin, hypertonic saline, isocapnic hyperpnea and cigarette
smoke. In rodent airways, the neurogenic plasma extravasation is mediated by
tachykinins released from the
capsaicin-afferent nerve fibres, and involves activation of neurokinin-1
tachykinin receptors. In peripheral guinea-pig airways, neurokinin-2
tachykinin receptors have also been implicated in the neurogenic plasma exudation. The
tachykinins can increase vascular permeability by both a direct effect on venular endothelium, and indirect mechanisms involving mast cell activation and
serotonin release.
Tachykinins and their receptors are present in the human airways. Release of
tachykinins, following
antigen challenge, has been demonstrated in the nose and lower airways. In humans,
tachykinins have been shown to increase plasma exudation in the nasal mucosa, but whether
neurogenic inflammation also occurs in the lower airways still remains to be proven.