Nearly fifty years ago, the existence of a "pain receptor" was postulated through which capsaicin could exert its "stimulatory and desensitizing" actions. More recently, that receptor, the transient receptor potential vanilloid 1 (TRPV1) has been molecularly cloned and characterized. Much research has been devoted to identify those molecules serving as endogenous agonists for TRPV1. Various eicosanoids may act as these so-called endovanilloids, but new, exciting findings indicate that oxidized metabolites of linoleic acid (OLAMs) satisfy a number of critical criteria to be classified as endogenous activators of TRPV1. Intriguingly, OLAMs may also participate as peripheral neurochemical conduits of heat itself. Thus, TRPV1 may not only be deorphanized, but OLAM "octadecadienoids" may represent a novel class of algogenic substances. These findings raise critical questions regarding the precise role(s) of TRPV1 in nociceptive transduction and about the importance of fatty acids in the modulation of pain and related functions. Moreover, these findings may inform the potential development of novel therapeutic strategies to treat pain.
ASJC Scopus subject areas
- Molecular Medicine