The TRPV1 ion channel: implications for respiratory sensation and dyspnea.

Unpleasant sensory and emotional experiences originating from the respiratory system, such as dyspnea, breathlessness, unsatisfied inspiration or air hunger are not immediately associated with nociceptive neurons, although they may be detected by the same class of C-fibre afferents. Nevertheless, the conceptual parallel between pain research, nociception and dyspnea is emerging as a paradigm that has the potential to identify novel molecular mechanisms contributing to dyspnea. Recent advances in pain biology such as the cloning of the transient receptor potential vanilloid 1 (TRPV1) ion channel, exploration of the molecular mechanisms leading to TRPV1 activation and the production of a TRPV1 mutant mouse have defined its role as an integrator of noxious thermal and chemical stimuli. These observations, coupled with the biology of lung C-fibre afferents and their reflex effects, suggest that TRPV1 may contribute to the multifactorial nature of dyspnea. The present review summarizes the properties of the TRPV1 ion channel known to be expressed in lung C-fibre afferents, the possible role of TRPV1 in respiratory sensation and neurogenic inflammation, as well as the limitations and opportunities associated with current TRPV1 antagonists.