Neurogenic inflammation of the airways and skin

Abstract

According to its original definition, the main feature of neurogenic inflammation is plasma leakage induced by the stimulation of peripheral sensory nerves. The plasma leakage from postcapillary venules is accompanied by increased blood flow due to dilatation of upstream arterioles, and by other phenomena, including leukocyte adhesion and migration. Neurogenic inflammation occurs in the airways, skin, and parts of the intestinal, urinary, and reproductive tract of man and animals, but varies markedly in its magnitude and extent. In skin, neurogenic inflammation is manifested as wheal and flare. Both phenomena are mediated by neuropeptides released from unmyelinated sensory nerve fibers via stimulation of capsaicin‐sensitive vanilloid receptors. Substance P is mainly responsible for the plasma leakage, acting via NK‐1 receptors present on target blood vessels, whereas calcitonin gene‐related peptide and substance P both induce vasodilatation. Sensory neuropeptides also trigger release of histamine from mast cells, which contributes substantially to plasma leakage in the skin, but less so in the airways. The increase in vascular permeability is due to a focal, transient, and fully reversible formation of gaps located between endothelial cell junctions. Neurogenic inflammation can be inhibited by preventing the stimulation of sensory nerves, by depleting them of their neuropeptide transmitters, by presynaptic inhibition of transmitter release, or by blocking neuropeptide receptors. Anti‐inflammatory drugs such as β‐adrenergic agonists and steroids can reduce neurogenic inflammation by stabilizing endothelial cells.