Commentary
Subject Category: Commentary
British Journal of Pharmacology (2008) 155, 1142–1144; doi:10.1038/bjp.2008.374; published online 10 November 2008
Hot target on nociceptors: perspectives, caveats and unique features
J Szolcsányi1
1Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Pécs, Hungary
Correspondence: Professor J Szolcsányi, Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, H-7624 Pécs, Szigeti u. 12., Hungary. E-mail: janos.szolcsanyi@aok.pte.hu
Received 9 September 2008; Accepted 20 September 2008; Published online 10 November 2008.
Abstract
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.
Keywords:
capsaicin, sensory-efferent function, C-polymodal nociceptor, resiniferatoxin, somatostatin, lipid raft, TRPV1 cation channel, thermosensor, nocisensor, sensocrine
Abbreviations:
TRPV1, transient receptor potential vanilloid-1


