Neuroeffector mechanisms: the interface between inflammation and neuronal responses

Abstract

There is a complex relation between inflammation and neural control of the airways. Cholinergic neurotransmission may be enhanced by inflammatory mediators; cholinergic nerves are the dominant neural pathway for bronchoconstriction in humans. Anticholinergic drugs are more effective in acute severe asthma than in chronic asthma, suggesting that cholinergic mechanisms may be important in exacerbations. Several possible abnormalities in adrenergic control in asthma have been proposed and may be caused by the inflammatory process. Adrenergic nerves do not have direct control of airway smooth muscle but may influence bronchomotor tone in several ways, such as adrenergic neural control of the bronchial vasculature or a secondary effect on cholinergic neurotransmission. Nonadrenergic noncholinergic (NANC) mechanisms mediate both bronchoconstriction and bronchodilation, and a defect in NANC bronchodilatation has been suggested to operate in severe asthma. Relatively little is known about the properties of airway sensory (afferent) nerves in human beings. They are thought to be involved in symptoms of cough and chest tightness, and the threshold for their activation is lowered in conditions of chronic inflammation. In addition, retrograde activation of sensory nerves by a local axon reflex, resulting in the release of peptides, may contribute to inflammation of the airways. Neurogenic inflammation is probably not relevant to mild asthma, however, but it may be more important in severe disease such as brittle asthma.