Physiology and plasticity of putative cough fibres in the Guinea pig

Pulm Pharmacol Ther. 2002;15(3):193-8. doi: 10.1006/pupt.2002.0362.


Cough is initiated by activation of afferent nerve fibers with rapidly adapting receptors (RAR) that conduct action potentials in the Adelta range. In addition, various stimuli that activate airway unmylenated C-fibres evoke cough reflexes. We have used a vagally innervated, larynx-trachea-bronchus preparation, isolated from guinea pigs, to study the pharmacology of RARs and C-fibres in vitro. In this preparation afferent fibres with the RAR phenotype are exquisitely sensitive to mechanical perturbation of their receptive fields, but are unaffected by a variety of mediators (e.g. prostaglandins, histamine, bradykinin, serotonin) and by capsaicin. By contrast, C-fibres are much less sensitive to mechanical stimulation, but can be activated by capsaicin and bradykinin. Preliminary evidence supports the hypothesis that bradykinin activate C-fibre by stimulating the capsaicin (vanilloid) receptor VR1. Acids activate both C-fibres and RARs. Acids stimulate RAR fibres by a mechanism that is rapidly inactivated. C-fibres are stimulated by both a rapidly inactivating mechanism, as well as a slowly inactivating mechanism. Drugs that block VR1 inhibit the latter mechanism. Airway inflammation substantially increases the mechanical sensitivity of RAR fibres without affecting their adaptive properties. Airway inflammation also causes a phenotypic switch in neuropeptide innervation of the airways that RAR neurons begin to synthesis neurokinins and calcitonin gene related peptide. In non-inflamed animals these peptides are expressed only in C-fibre neurons. Thus, airway inflammation may not only increase the sensitivity of cough fibres, but may also qualitatively change the role played by sensory neuropeptides in cough reflexes.

Publication types

  • Review

MeSH terms

  • Animals
  • Bradykinin / pharmacology
  • Capsaicin / pharmacology
  • Citric Acid / pharmacology
  • Cough / physiopathology*
  • Guinea Pigs
  • Neuronal Plasticity / physiology*
  • Neurons, Afferent / physiology
  • Vagus Nerve / physiology*


  • Citric Acid
  • Capsaicin
  • Bradykinin