The analgesic properties of camphor, a plant-derived product with a long history of medical use, might reflect its effects on at least two types of TRP (transient receptor potential) ion channel, according to a recent report from David Clapham's laboratory.
The six subfamilies of TRP ion channels have diverse roles as cellular sensors. Thermosensitive TRP channels detect a wide range of temperatures, including cool and warmth, and noxious cold and heat. In addition, all thermoTRP channels seem to be chemosensitive. For example, the vanilloid receptor TRPV1 is stimulated by heat and by capsaicin (the 'hot' ingredient in chilli peppers), the analgesic effects of which are probably due, at least in part, to channel desensitization.
Camphor is commonly applied to the skin for analgesic, antipruritic and counter-irritant purposes, but its molecular and cellular targets are largely unknown. Camphor was recently shown to activate TRPV3 in epithelial keratinocytes, and is known to produce a warm sensation, in keeping with the thermal activation range of this thermoTRP. But repeated applications of camphor led to TRPV3 sensitization, apparently contradicting camphor's analgesic role.
Xu and colleagues now report that camphor activates TRPV1 in a manner that is independent of the vanilloid (capsaicin) binding site, and inhibits ankyrin-repeat TRP 1 (TRPA1). Both of these thermoTRPs are abundant in nociceptive dorsal root ganglion (DRG) neurons. Camphor-evoked TRPV1-like currents recorded from rat DRG neurons were strongly potentiated after a manipulation that mimicked peripheral sensitization, which suggests that the use of camphor to treat irritated or inflamed skin might be related to its increased efficacy in these states.
Among TRPV1 agonists, Xu et al. showed that camphor has exceptionally strong desensitizing properties. The combined desensitization of TRPV1 and inhibition of TRPA1 provides a new explanation for the analgesic properties of this age-old remedy.
ORIGINAL RESEARCH PAPER
Xu, H. et al. Camphor activates and strongly desensitizes the transient receptor potential vanilloid subtype 1 channel in a vanilloid-independent mechanism. J. Neurosci. 25, 8924–8937 (2005)
Moqrich, A. et al. Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin. Science 307, 1468–1472 (2005)