Abstract
Chronic cough is common in the population, and among some there is no evident medical explanation for the symptoms. Such a refractory or idiopathic cough is now often regarded as a neuropathic disease due to dysfunctional airway ion channels, though the knowledge in this field is still limited. Persistent coughing and a cough reflex easily triggered by irritating stimuli, often in combination with perceived dyspnea, are characteristics of this disease. The patients have impaired quality of life and often reduced work capacity, followed by social and economic consequences. Despite the large number of individuals suffering from such a persisting cough, there is an unmet clinical need for effective cough medicines. The cough treatment available today often has little or no effect. Adverse effects mostly follow centrally acting cough drugs comprised of morphine and codeine, which demands the physician’s awareness. The possibilities of modulating airway transient receptor potential (TRP) ion channels may indicate new ways to treat the persistent cough “without a reason”. The TRP ion channel vanilloid 1 (TRPV1) and the TRP melastin 8 (TRPM8) appear as two candidates in the search for cough therapy, both as single targets and in reciprocal interaction.
Highlights
It is better understood today, the theoretical explanation as to why menthol has an ameliorating effect on cough reflex sensitivity remains in part obscure, but acting via TRP melastin 8 (TRPM8), menthol may interfere with TRP ion channel vanilloid 1 (TRPV1) and the cough outcome from capsaicin and environmental irritants [34,35]
A new paradigm has been developed of chronic idiopathic cough (CIC) as a possible neuropathic disease that could be linked to the transient receptor potential (TRP) ion channels, with persisting cough as an unmistakable symptom
The results could suggest that TRPV1 may not be of such great importance in chronic cough as earlier believed, but the evident relation between chronic cough, TRPV1 expression and cough sensitivity to inhaled capsaicin contradicts such a paradigm change
Summary
Coughing by humans is a necessary protective mechanism to prohibit food and foreign substances from reaching and harming the lower airways. The symptoms mimic asthma, but asthma-specific tests are negative These patients have an increased cough reaction to inhaled capsaicin (the active compound of chili peppers), a tasteless and odorless substance that stimulates sensory nerves, and the provoked cough reflects sensory nerve reactivity [13]. Such airway symptoms are interpreted as airway sensory hyperreactivity (SHR). The patients could be diagnosed with CIC [14] or the recently established cough hypersensitivity syndrome (CHS) [15] This syndrome includes several airway conditions characterized by evoked cough reflex and increased cough sensitivity to inhaled capsaicin [15,16,17,18]. There was a high degree of agreement in a recent article reporting how opinion leaders in cough research regarded the suggestion of CHS as a cause underlying the cough etiology in CIC [19], and it is today, together with some forms of itch and pain [20], regarded as a possible neuropathic disease following neural injuries from various inflammatory, infective, and irritative influences [21,22,23]
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