Neurogenic inflammation in lung disease: Burnt out?

Abstract

Neurogenic inflammation results from activation of sensory nerves which, acting in an 'efferent' manner, release sensory neuropeptides to induce a wide variety of physiological and immunological responses. This process is easy to demonstrate experimentally in the airways of small laboratory animal species but in human airways is equivocal and, at best, minor compared with cholinergic neural control. Nevertheless, sensory neuropeptides (calcitonin gene-related peptide and the tachykinins, substance P and neurokinin A) induce airway responses in both laboratory animals and humans which suggest a potential for sensory-efferent control of human airways. In addition, there is indirect evidence for an increased 'expression' of sensory nerves and tachykinin receptors in asthma and bronchitis, which indicates that neurogenic inflammation contributes to pathophysiology of these airway conditions. In contrast, clinical trials using different classes of drugs to inhibit sensory nerve responses have failed to resolve whether neurogenic inflammation is involved in asthma, although there are concerns about the relevance of some of these studies. In contrast to their involvement in airway neurogenic inflammation, sensory nerves may be important in initiating protective reflexes, including coughing and sneezing, acting via their afferent pathways. Thus, although flickering, the concept of neurogenic inflammation in lung disease is not yet burnt out. However, it needs the rekindling of interest which re-evaluation as a protective process may bring, together with data from more appropriate clinical studies in asthma and chronic bronchitis.

Effect of the long‐acting tachykinin NK1 receptor antagonist MEN 11467 on tracheal mucus secretion in allergic ferrets

“…Inhibition of tachykininergic mucus secretion has clinical implications. For example, although to date substantially unproven, tachykinins have been implicated in the pathophysiology of asthma and COPD ( Rogers, 1997 ; Barnes, 1998 ), and in the development of bronchial hyperresponsiveness, an important clinical feature of asthma ( Spina et al ., 1998 ). In both asthma and COPD, airway mucus hypersecretion is a significant component of morbidity and mortality ( Liu et al ., 1998a ; Rogers, 2000b ).…”

Capsaicin‐induced mucus secretion in rat airways assessed in vivo and non‐invasively by magnetic resonance imaging

“…An upregulation of sensory‐efferent neural pathways is also implicated in COPD and asthma ( Rogers, 1997 ). Airway sensory nerves release several neuropeptides of which the tachykinins (neurokinin A (NKA) and substance P (SP)) contribute most to the pathophysiology of asthma and COPD ( Joos et al ., 2003 ).…”