Noxious heat activates all capsaicin-sensitive and also a sub-population of capsaicin-insensitive dorsal root ganglion neurons

A sub-population of primary afferent fibres comprising mainly Adelta and C polymodal nociceptors specifically detects high intensity heat stimuli. These fibres are also sensitive to high threshold mechanical stimulation and different chemicals including inflammatory mediators. C-polymodal nociceptors are also activated by capsaicin. Recent findings show that noxious heat induces inward currents in a sub-population of cultured dorsal root ganglion neurons by opening nonselective cation-channels. It has been suggested that noxious heat is transduced by the recently cloned capsaicin-gated ion-channel since oocytes and HEK 293 cells expressing this channel respond to heat as well as capsaicin. In agreement with this suggestion Kirschstein et al. found in a small sample of dorsal root ganglion cells that all heat-sensitive neurons were also sensitive to capsaicin. In this study we examine further, by whole-cell voltage-clamp recording from adult rat dorsal root ganglion neurons grown in culture, the relationship between heat- and capsaicin-sensitivity. Our results show the existence of two kinds of heat-sensitive neurons, distinguished by their temperature thresholds. The low-threshold cells, which comprise the small-medium diameter population, are capsaicin-sensitive, whereas the high-threshold (mainly large-diameter) cells are not, and we postulate the existence of a heat transducer distinct from capsaicin receptor in the latter group.