Sensing pulmonary oxidative stress by lung vagal afferents

Respir Physiol Neurobiol. 2011 Sep 30;178(3):406-13. doi: 10.1016/j.resp.2011.05.003. Epub 2011 May 10.


Oxidative stress in the bronchopulmonary airways can occur through a variety of inflammatory mechanisms and also following the inhalation of environmental pollutants. Oxidative stress causes cellular dysfunction and thus mammals (including humans) have developed mechanisms for detecting oxidative stress, such that defensive behavior and defensive biological mechanisms can be induced to lessen its potential damage. Vagal sensory nerves innervating the airways play a critical role in the detection of the microenvironment in the airways. Oxidative stress and associated compounds activate unmyelinated bronchopulmonary C-fibers, initiating action potentials in these nerves that conduct centrally to evoke unpleasant sensations (e.g. urge to cough, dyspnea, chest-tightness) and to stimulate/modulate reflexes (e.g. cough, bronchoconstriction, respiratory rate, inspiratory drive). This review will summarize the published evidence regarding the mechanisms by which oxidative stress, reactive oxygen species, environmental pollutants and lipid products of peroxidation activate bronchopulmonary C-fibers. Evidence suggests a key role for transient receptor potential ankyrin 1 (TRPA1), although transient receptor potential vanilloid 1 (TRPV1) and purinergic P2X channels may also play a role. Knowledge of these pathways greatly aids our understanding of the role of oxidative stress in health and disease and represents novel therapeutic targets for diseases of the airways.

Publication types

  • Review

MeSH terms

  • Afferent Pathways / physiology
  • Afferent Pathways / physiopathology
  • Animals
  • Humans
  • Lung / innervation*
  • Lung / physiopathology
  • Lung Diseases / etiology*
  • Lung Diseases / metabolism
  • Lung Diseases / physiopathology*
  • Oxidative Stress / physiology*
  • Reactive Oxygen Species / metabolism
  • Vagus Nerve / physiology*
  • Vagus Nerve / physiopathology


  • Reactive Oxygen Species