Identification of the tracheal and laryngeal afferent neurones mediating cough in anaesthetized guinea‐pigs

We have identified the tracheal and laryngeal afferent nerves regulating cough in anaesthetized guinea‐pigs. Cough was evoked by electrical or mechanical stimulation of the tracheal or laryngeal mucosa, or by citric acid applied topically to the trachea or larynx. By contrast, neither capsaicin nor bradykinin challenges to the trachea or larynx evoked cough. Bradykinin and histamine administered intravenously also failed to evoke cough. Electrophysiological studies revealed that the majority of capsaicin‐sensitive afferent neurones (both Aδ‐ and C‐fibres) innervating the rostral trachea and larynx have their cell bodies in the jugular ganglia and project to the airways via the superior laryngeal nerves. Capsaicin‐insensitive afferent neurones with cell bodies in the nodose ganglia projected to the rostral trachea and larynx via the recurrent laryngeal nerves. Severing the recurrent nerves abolished coughing evoked from the trachea and larynx whereas severing the superior laryngeal nerves was without effect on coughing. The data indicate that the tracheal and laryngeal afferent neurones regulating cough are polymodal Aδ‐fibres that arise from the nodose ganglia. These afferent neurones are activated by punctate mechanical stimulation and acid but are unresponsive to capsaicin, bradykinin, smooth muscle contraction, longitudinal or transverse stretching of the airways, or distension. Comparing these physiological properties with those of intrapulmonary mechanoreceptors indicates that the afferent neurones mediating cough are quite distinct from the well‐defined rapidly and slowly adapting stretch receptors innervating the airways and lungs. We propose that these airway afferent neurones represent a distinct subtype and that their primary function is regulation of the cough reflex.

[1]  D. Weinreich,et al.  Subtypes of vagal afferent C‐fibres in guinea‐pig lungs , 2004, The Journal of physiology.

[2]  M. Kollarik,et al.  Mechanisms of acid‐induced activation of airway afferent nerve fibres in guinea‐pig , 2002, The Journal of physiology.

[3]  S. Mazzone,et al.  An in vivo guinea pig preparation for studying the autonomic regulation of airway smooth muscle tone , 2002, Autonomic Neuroscience.

[4]  S. Mazzone,et al.  Synergistic interactions between airway afferent nerve subtypes mediating reflex bronchospasm in guinea pigs. , 2002, American journal of physiology. Regulatory, integrative and comparative physiology.

[5]  B. Canning Interactions between vagal afferent nerve subtypes mediating cough. , 2002, Pulmonary pharmacology & therapeutics.

[6]  S. Mazzone,et al.  Multiple mechanisms of reflex bronchospasm in guinea pigs. , 2001, Journal of applied physiology.

[7]  Q. Gu,et al.  Sensitivity of vagal afferent endings to chemical irritants in the rat lung. , 2001, Respiration physiology.

[8]  E S Schelegle,et al.  An overview of the anatomy and physiology of slowly adapting pulmonary stretch receptors. , 2001, Respiration physiology.

[9]  L. Lee,et al.  Afferent properties and reflex functions of bronchopulmonary C-fibers. , 2001, Respiration physiology.

[10]  S. Aoyagi,et al.  Participation of thromboxane A2 in the cough response in guinea‐pigs: antitussive effect of ozagrel , 2000, British journal of pharmacology.

[11]  M. McAlexander,et al.  Adaptation of guinea‐pig vagal airway afferent neurones to mechanical stimulation , 1999, The Journal of physiology.

[12]  R. Fuller,et al.  Pharmacological regulation of the cough reflex--from experimental models to antitussive effects in Man. , 1999, Pulmonary pharmacology & therapeutics.

[13]  B. Undem,et al.  Identification and substance P content of vagal afferent neurons innervating the epithelium of the guinea pig trachea. , 1999, American journal of respiratory and critical care medicine.

[14]  D. Proud,et al.  Characterization of vagal afferent subtypes stimulated by bradykinin in guinea pig trachea. , 1999, The Journal of pharmacology and experimental therapeutics.

[15]  M. Hashimoto,et al.  Effects of moguisteine on the cough reflex induced by afferent electrical stimulation of the superior laryngeal nerve in guinea pigs. , 1998, European journal of pharmacology.

[16]  J. Widdicombe Afferent receptors in the airways and cough. , 1998, Respiration physiology.

[17]  V. Lagente,et al.  The role of tachykinin receptor antagonists in the prevention of bronchial hyperresponsiveness, airway inflammation and cough. , 1997, The European respiratory journal.

[18]  T. Miyata,et al.  Differential effect of codeine on coughs caused by mechanical stimulation of two different sites in the airway of guinea pigs. , 1997, European journal of pharmacology.

[19]  D. Bergren Sensory receptor activation by mediators of defense reflexes in guinea-pig lungs. , 1997, Respiration physiology.

[20]  J. Hey,et al.  Central antitussive activity of the NK1 and NK2 tachykinin receptor antagonists, CP‐99,994 and SR 48968, in the guinea‐pig and cat , 1997, British journal of pharmacology.

[21]  W. Kummer,et al.  Interganglionic segregation of distinct vagal afferent fibre phenotypes in guinea‐pig airways. , 1996, The Journal of physiology.

[22]  R. Pecova,et al.  The role of partial laryngeal denervation on the cough reflex in awake guinea-pigs, rats and rabbits. , 1996, Pulmonary pharmacology.

[23]  K. Chung,et al.  Capsazepine inhibits cough induced by capsaicin and citric acid but not by hypertonic saline in guinea pigs. , 1995, Journal of applied physiology.

[24]  M. Tatar,et al.  Laryngeal and tracheobronchial cough in anesthetized dogs. , 1994, Journal of applied physiology.

[25]  A. Fox,et al.  An in vitro study of the properties of single vagal afferents innervating guinea‐pig airways. , 1993, The Journal of physiology.

[26]  C. Gallagher,et al.  Lack of importance of the superior laryngeal nerves in citric acid cough in humans. , 1993, Journal of applied physiology.

[27]  R. Eccles,et al.  Voluntary suppression of cough induced by inhalation of capsaicin in healthy volunteers. , 1993, Respiratory medicine.

[28]  H. Tsubone,et al.  Vagal afferent activities and respiratory reflexes during drug-induced bronchoconstriction in the guinea pig. , 1992, The Journal of veterinary medical science.

[29]  T. Miyata,et al.  Neurokinin A, but not neurokinin B and substance P, induces codeine-resistant coughs in awake guinea-pigs , 1992, Regulatory Peptides.

[30]  W. Kummer,et al.  The sensory and sympathetic innervation of guinea-pig lung and trachea as studied by retrograde neuronal tracing and double-labelling immunohistochemistry , 1992, Neuroscience.

[31]  M. Fujimura,et al.  Effects of methacholine induced bronchoconstriction and procaterol induced bronchodilation on cough receptor sensitivity to inhaled capsaicin and tartaric acid. , 1992, Thorax.

[32]  G. Orani,et al.  Laryngeal afferent activity and reflexes in the guinea pig. , 1991, Respiration physiology.

[33]  D. Bolser,et al.  Ruthenium red decreases capsaicin and citric acid-induced cough in guinea pigs , 1991, Neuroscience Letters.

[34]  J. Kohl,et al.  Location of pulmonary stretch receptors in the guinea-pig. , 1989, Respiration physiology.

[35]  M. Tatar,et al.  Lung C‐fibre receptor activation and defensive reflexes in anaesthetized cats. , 1988, The Journal of physiology.

[36]  R. Pauwels,et al.  Effect of inhaled substance P and neurokinin A on the airways of normal and asthmatic subjects. , 1987, Thorax.

[37]  J. Karlsson,et al.  Cough induced by stimulation of capsaicin-sensitive sensory neurons in conscious guinea-pigs. , 1986, Acta physiologica Scandinavica.

[38]  N. Barnes,et al.  Comparative effects of inhaled leukotriene C4, leukotriene D4, and histamine in normal human subjects. , 1984, Thorax.

[39]  J. Widdicombe Respiratory reflexes excited by inflation of the lungs , 1954, The Journal of physiology.

[40]  J. Widdicombe Receptors in the trachea and bronchi of the cat , 1954, The Journal of physiology.

[41]  J. Widdicombe Respiratory reflexes from the trachea and bronchi of the cat , 1954, The Journal of physiology.

[42]  J. Widdicombe Functional morphology and physiology of pulmonary rapidly adapting receptors (RARs). , 2003, The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology.

[43]  H. Sarau,et al.  Nonpeptide tachykinin receptor antagonists. III. SB 235375, a low central nervous system-penetrant, potent and selective neurokinin-3 receptor antagonist, inhibits citric acid-induced cough and airways hyper-reactivity in guinea pigs. , 2002, The Journal of pharmacology and experimental therapeutics.

[44]  K. Ravi,et al.  Properties of rapidly adapting receptors of the airways in monkeys (Macaca mulatta). , 1995, Respiration physiology.

[45]  H. Coleridge,et al.  Pulmonary reflexes: neural mechanisms of pulmonary defense. , 1994, Annual review of physiology.

[46]  M. Dahlbäck,et al.  Regional sensitivity of the respiratory tract to stimuli causing cough and reflex bronchoconstriction. , 1991, Respiratory Medicine.

[47]  S. Sampson,et al.  Characterization of intrapulmonary, rapidly adapting receptors of guinea pigs. , 1982, Respiration physiology.

[48]  Non-peptide tachykinin receptor antagonists , 1994 .