In the respiratory tract, TRPV1, a non-selective
cation channel and a polymodal transducer, is expressed primarily in non-myelinated sensory nerves. A significant role of TRPV1 in eliciting the
cough reflex has been extensively documented. Inhalation of
capsaicin aerosol, a selective agonist of TRPV1, consistently and reproducibly evoked
coughs in a dose-dependent manner in both healthy humans and in patients with airway inflammatory diseases. A number of endogenous inflammatory mediators known to upregulate the TRPV1 sensitivity, such as
prostaglandin E(2) and
bradykinin, also enhanced the
cough sensitivity. Furthermore, a substantial increase of TRPV1-immunoreactive nerve profiles was found in the bronchial tissue of patients with
chronic cough. In addition to the
cough reflex, activation of TRPV1-expressing sensory nerves in the airways is also known to elicit reflex bronchoconstriction and mucus secretion mediated through
cholinergic pathways. One of the physiological stimuli known to activate
TRPV1 receptor directly is high temperature. Recent studies have demonstrated that increasing temperature within the normal physiological range significantly elevated the baseline activity and sensitivity of isolated rat vagal pulmonary sensory neurons, and the sensitizing effect of
hyperthermia appeared to be mediated selectively through the TRPV1 channel. This temperature-sensitive property of TRPV1 may play an important role in regulating the physiological function of the TRPV1-expressing airway sensory nerves and the sensitivity of their reflex responses, such as
cough and reflex bronchoconstriction.