Inflammation-induced plasticity of the afferent innervation of the airways

The activation of primary afferent neurons that innervate the airways leads to homeostatic and defensive reflexes. The anatomic and physiologic charac teristics of these afferent fibers do not appear to be static properties bu t rather appear to change rapidly in response to inflammation. The threshol d for activation of airway afferent neurons to various stimuli, for example , is not fixed; these fibers can be become sensitized during inflammation. A subset of nociceptive-like (C-fibers) airway afferent neurons not only pa rticipates in centrally mediated reflexes but is also thought to release ne uropeptides at their peripheral terminals, leading to neurogenic inflammati on. An increase in the content of tachykinins is commonly seen in inflamed tissues, and there is accumulating evidence that irritation and inflammatio n of the airways is associated with the induction of tachykinin synthesis i n non-nociceptive airway afferent fibers that under normal conditions do no t contain neuropeptides. The release of neurokinins from the peripheral ter minals in the airways and their central terminals in the brain stem may con tribute to the symptoms of inflammatory airway diseases. Elevated release o f neurokinins from peripheral terminals may promote local inflammatory resp onses, and the release of neurokinins in the brainstem, together with infla mmation-induced increases in the excitability of afferent fibers, may culmi nate in altered visceral autonomic reflex activity, changes in breathing pa ttern, and cough.