Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia

The vanilloid receptor-1 (VR1) is a ligand-gated, non-selective cation chan nel expressed predominantly by sensory neurons. VR1 responds to noxious sti muli including capsaicin, the pungent component of chilli peppers, heat and extracellular acidification, and it is able to integrate simultaneous expo sure to these stimuli(1,2). These findings and research linking capsaicin w ith nociceptive behaviours (that is, responses to painful stimuli in animal s(3) have led to VR1 being considered as important for pain sensation. Here we have disrupted the mouse VR1 gene using standard gene targeting techniq ues. Small diameter dorsal root ganglion neurons isolated from VR1-null mic e lacked many of the capsaicin-, acid- and heat-gated responses that have b een previously well characterized in small diameter dorsal root ganglion ne urons from various species. Furthermore, although the VR1-null mice appeare d normal in a wide range of behavioural tests, including responses to acute noxious thermal stimuli, their ability to develop carrageenan-induced ther mal hyperalgesia was completely absent. We conclude that VR1 is required fo r inflammatory sensitization to noxious thermal stimuli but also that alter native mechanisms are sufficient for normal sensation of noxious heat.