Hot target on nociceptors: perspectives, caveats and unique features.

Identification of C-polymodal nociceptors and the selective action of capsaicin on them by acting on a putative receptor, which has been cloned 11 years ago, initiated a burst of interest in pharmacology of nociceptors. Capsaicin receptor transient receptor potential vanilloid-1 (TRPV1) being a noxious heat-gated cation channel gated also by several exogenous and endogenous substances serves as a nocisensor to generate graded receptor potentials in these sense organs. Impressive data on pathways involved in sensitization/desensitization of the channel revealed in isolated cells should also validate at the level of nerve endings and lipid raft around TRPV1 could modify the channel gating. Capsaicin-sensitive nociceptors subserve dual sensory-efferent functions: tachykinins and calcitonin gene-related peptide released from them elicit local tissue responses as neurogenic inflammation and release of somatostatin evokes systemic anti-inflammatory and antihyperalgesic effects. TRPV1 gene-deleted mice show subtle changes in physiological regulations, therefore TRPV1 is a promising but challenging target for drug research.