Opposing effects of bronchopulmonary C-fiber subtypes on cough in guinea pigs

Am J Physiol Regul Integr Comp Physiol. 2018 Mar 1;314(3):R489-R498. doi: 10.1152/ajpregu.00313.2017. Epub 2017 Nov 29.


We have addressed the hypothesis that the opposing effects of bronchopulmonary C-fiber activation on cough are attributable to the activation of C-fiber subtypes. Coughing was evoked in anesthetized guinea pigs by citric acid (0.001-2 M) applied topically in 100-µl aliquots to the tracheal mucosa. In control preparations, citric acid evoked 10 ± 1 coughs cumulatively. Selective activation of the pulmonary C fibers arising from the nodose ganglia with either aerosols or continuous intravenous infusion of adenosine or the 5-HT3 receptor-selective agonist 2-methyl-5-HT nearly abolished coughing evoked subsequently by topical citric acid challenge. Delivering adenosine or 2-methyl-5-HT directly to the tracheal mucosa (where few if any nodose C fibers terminate) was without effect on citric acid-evoked cough. These actions of pulmonary administration of adenosine and 2-methyl-5-HT were accompanied by an increase in respiratory rate, but it is unlikely that the change in respiratory pattern caused the decrease in coughing, as the rapidly adapting receptor stimulant histamine also produced a marked tachypnea but was without effect on cough. In awake guinea pigs, adenosine failed to evoke coughing but reduced coughing induced by the nonselective C-fiber stimulant capsaicin. We conclude that bronchopulmonary C-fiber subtypes in guinea pigs have opposing effects on cough, with airway C fibers arising from the jugular ganglia initiating and/or sensitizing the cough reflex and the intrapulmonary C fibers arising from the nodose ganglia actively inhibiting cough upon activation.

Keywords: adenosine; bradykinin; capsaicin; jugular; nodose; serotonin.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials
  • Adenosine / administration & dosage
  • Animals
  • Bradykinin / administration & dosage
  • Citric Acid
  • Cough / chemically induced
  • Cough / physiopathology*
  • Cough / prevention & control
  • Disease Models, Animal
  • Guinea Pigs
  • Histamine / administration & dosage
  • Male
  • Nerve Fibers, Unmyelinated / classification*
  • Nerve Fibers, Unmyelinated / drug effects
  • Nodose Ganglion / drug effects
  • Nodose Ganglion / physiopathology*
  • Purinergic P1 Receptor Agonists / administration & dosage
  • Reflex
  • Respiratory Rate
  • Serotonin / administration & dosage
  • Serotonin / analogs & derivatives
  • Serotonin 5-HT3 Receptor Agonists / administration & dosage
  • Trachea / innervation*


  • Purinergic P1 Receptor Agonists
  • Serotonin 5-HT3 Receptor Agonists
  • Citric Acid
  • Serotonin
  • 2-methyl-5-HT
  • Histamine
  • Adenosine
  • Bradykinin