title: Irritant-induced chronic cough: irritant-induced TRPpathy.
abstract: This article expands the author's presentation at the First American Cough Conference in New York City, June 8-9, 2007. The results of a scientific literature search and application of personal research findings are included. A new hypothesis to explain irritant-induced cough as a being a dysfunction of the transient receptor potential vanilloid 1 (TRPV1) cation channels located in pulmonary excitable cells is presented. The TRPV1 cation channels regulate cellular transmembrane voltage by raising intracellular Ca(2+) and Na(+) concentrations and depolarizing sensory nerve cells containing C-fibers. The discussion centers on the "capsaicin receptor" (TRPV1) and another important ion channel, TRPA1. The author reviews results of published scientific investigations to support his contention that neural events, initiated by TRPV1 ion channels, lead to a cascade of alterations that progress to a cough endpoint. A potential mechanism to explain chronic cough in conditions where there is repeated or severe irritant-induced airway epithelial injury (e.g., RADS) is through persistent TRPV1 channel activation (e.g., TRPV1pathy) with accumulation of inflammatory mediators, tachykinins, and the release of neurotrophins leading to persistent cough and airway inflammation. The significance of the hypothesis is that, if proven, it may provide new therapeutic approaches for the treatment of chronic cough.
authors.affiliation: Colleges of Public Health, University of South Florida, Tampa, FL 33612, USA. sbrooks@hsc.usf.edu
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Brooks
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002211:Capsaicin / Q000627:therapeutic use; D002908:Chronic Disease; D003371:Cough / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007509:Irritants / Q000009:adverse effects* / Q000633:toxicity; D008168:Lung / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism; D012018:Reflex / Q000187:drug effects; D018689:Sensory System Agents / Q000627:therapeutic use*; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000187:drug effects / Q000378:metabolism*; D050051:Transient Receptor Potential Channels / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D015220:Calcium Channels; D007509:Irritants; D009419:Nerve Tissue Proteins; D018689:Sensory System Agents; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D050051:Transient Receptor Potential Channels; D002211:Capsaicin