The Role of Vagal Afferent Nerves in Chronic Obstructive Pulmonary Disease

Circumstantial evidence supports the hypothesis that the vagal nervous system is dysregulated in chronic obstructive pulmonary disease. This dysregulation can lead to an increased sensitivity of the cough reflex such that the coughing becomes, at times, “nonproductive” or inappropriate. Vagal dysregulation can also lead to an increase in the activity of the parasympathetic reflex control of the airways, which contributes to greater mucus secretion and bronchial smooth muscle contraction. Indirect evidence indicates that lung disease is accompanied by substantive changes to the entire reflex pathways, including enhanced activity of the primary afferent nerves, increases in synaptic efficacy at secondary nerves in the central nervous system, and changes in the autonomic nerve pathways. Drugs aimed at normalizing neuronal activity may, therefore, be beneficial in chronic obstructive pulmonary disease

Capsaicin-sensitive and -insensitive vagal bronchopulmonary C-fibres in the mouse

We developed an isolated tracheally perfused (35–37 °C) nerve-lung preparation for the study of bronchopulmonary afferent nerve activity in the mouse. Extracellular recordings were made from the vagal sensory neurons located in the jugular-nodose ganglia complex (JNC) with identified receptive fields in the lungs. Analysis of the vagal compound action potential revealed that the mouse vagal C-fibre conduction velocities range from 0.3 to 1.5 m s−1. A total of 83 bronchopulmonary C-fibres were studied. The sensitivity of the bronchopulmonary C-fibres to the vanilloid receptor 1 (VR1) agonist capsaicin was dependent on conduction velocity. Thus C-fibres with conduction velocities between 0.3 and 0.7 m s−1 responded to capsaicin (1 μM) while C-fibres with conduction velocities between 0.7 and 1.5 m s−1 were capsaicin insensitive. Similarly, bradykinin (1 μM) excited only those C-fibres with conduction velocities < 0.7 m s−1. The response to bradykinin was not mimicked by the B1 receptor agonist [des-Arg9]bradykinin (1 μM) and was abolished by the bradykinin B2 receptor antagonist HOE 140 (1 μM). Adenosine 5′-triphosphate (ATP, 30 μM) activated the C-fibres irrespective of the conduction velocities. This response was mimicked by the selective P2X agonist α,β-methylene-adenosine 5′-triphosphate (30 μM). Consistent with the electrophysiology, morphological analysis revealed that only ˜40 % of the lung-specific small diameter (< 20 μm) JNC neurons consistent with the C-fibre cell bodies display VR1 immunoreactivity. This study describes a convenient in vitro method for the study of mouse bronchopulmonary C-fibres. The results indicate that C-fibres in the mouse lungs are not homogeneous, but can be subclassified into capsaicin-sensitive and capsaicin-insensitive phenotypes