Capsaicin-sensitive nerve endings

TRPVl also plays a central role in intercellular pro-inflammatory feedback loops. An important example is mast cells and sensory nerves. Mast cells release tryptase that, in turn, activates the protease-activated receptor PAR-2 activation of PAR-2 then opens TRPVl via PKC [50]. In keeping with this, PAR-2 agonists reduce the heat activation threshold of TRPVl from 42 °C to below body temperature [51]. Excited nerve endings release SP that, as a positive feedback, binds to neurokinin NKl receptors on mast cells. Mast cells also express TRPVl [52]. Consequently, endovanilloids can act in concert to stimulate mast cells and activate capsaicin-sensitive nerve endings. Of relevance is the finding that PAR-2 is up-regulated in the bladder during experimental cystitis [53]. 

The role of peptidergic neurons is not so clear. Capsaicin, the hot chile pepper chemical that evokes release of peptide transmitters from several types of sensory nerves, has been shown to reproduce some of the signs of bronchial hyperreactivity in animal and human experiments. These findings led to the proposal that sensitization of afferent nerve endings played a major role in chronic airway hyperreactivity. However, peptide transmitter antagonists have not been able to prevent bronchoconstriction in several models. Clearly, much remains to be learned about airway pharmacology. 

---