Increased expression of transient receptor potential vanilloid-1 in airway nerves of chronic cough.

Transient receptor potential vanniloid-1 (TRPV-1) mediates the cough response induced by the pepper extract capsaicin and is expressed in sensory nerves that innervate the airway wall. We determined the expression of TRPV-1 in the airways of patients with chronic persistent cough of diverse causes and with an enhanced capsaicin cough response. We obtained airway mucosal biopsies by fiberoptic bronchoscopy in 29 patients with chronic cough and 16 healthy volunteers without a cough. Immunostaining for nerve profiles with anti-protein gene product (PGP)-9.5 antibody showed no increase in nerve profiles in the airway epithelium of patients with chronic cough; however, with an anti-TRPV-1 antibody, there was a fivefold increase of TRPV-1 staining nerve profiles (p < 0.001). There was a significant correlation between capsaicin tussive response and the number of TRPV-1-positive nerves within the patients with cough. Our findings indicate that TRPV-1 receptors may contribute to an enhanced cough reflex and the cough response in chronic persistent cough of diverse causes.

[1]  K. Chung,et al.  Reduced pH and chloride levels in exhaled breath condensate of patients with chronic cough , 2004, Thorax.

[2]  R. Egan,et al.  Anandamide induces cough in conscious guinea‐pigs through VR1 receptors , 2002, British journal of pharmacology.

[3]  K. Chung.  Cough: potential pharmacological developments , 2002, Expert opinion on investigational drugs.

[4]  Uhtaek Oh,et al.  Hot channels in airways: pharmacology of the vanilloid receptor. , 2002, Current opinion in pharmacology.

[5]  P. Anand,et al.  Vanilloid receptor 1 immunoreactivity in inflamed human bowel , 2001, The Lancet.

[6]  T. Sugimoto,et al.  VR1-immunoreactive primary sensory neurons in the rat trigeminal ganglion , 2001, Brain Research.

[7]  P. Pasricha,et al.  Nerve growth factor regulates VR-1 mRNA levels in cultures of adult dorsal root ganglion neurons , 2001, Pain.

[8]  L. Premkumar,et al.  Induction of vanilloid receptor channel activity by protein kinase C , 2000, Nature.

[9]  R. Irwin,et al.  The diagnosis and treatment of cough. , 2000, The New England journal of medicine.

[10]  P. Zygmunt,et al.  The anandamide transport inhibitor AM404 activates vanilloid receptors. , 2000, European journal of pharmacology.

[11]  D. Julius,et al.  Acid potentiation of the capsaicin receptor determined by a key extracellular site. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[12]  G. Michael,et al.  Differential Expression of the mRNA for the Vanilloid Receptor Subtype 1 in Cells of the Adult Rat Dorsal Root and Nodose Ganglia and Its Downregulation by Axotomy , 1999, The Journal of Neuroscience.

[13]  A. Basbaum,et al.  The Cloned Capsaicin Receptor Integrates Multiple Pain-Producing Stimuli , 1998, Neuron.

[14]  D. Julius,et al.  The capsaicin receptor: a heat-activated ion channel in the pain pathway , 1997, Nature.

[15]  R. Quirion,et al.  Calcitonin gene-related peptide in viscerosensitive response to colorectal distension in rats. , 1997, The American journal of physiology.

[16]  K. Chung,et al.  Diagnosis and management of chronic persistent dry cough. , 1996, Postgraduate medical journal.

[17]  N. Pride,et al.  Abnormal intraepithelial airway nerves in persistent unexplained cough? , 1995, American journal of respiratory and critical care medicine.

[18]  J. Widdicombe,et al.  Neurophysiology of the cough reflex. , 1995, The European respiratory journal.

[19]  N. Pride,et al.  Capsaicin cough sensitivity decreases with successful treatment of chronic cough. , 1994, American journal of respiratory and critical care medicine.

[20]  N. Choudry,et al.  Sensitivity of the cough reflex in patients with chronic cough. , 1992, The European respiratory journal.

[21]  R. Irwin,et al.  Chronic cough. The spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy. , 1990, The American review of respiratory disease.