The transient receptor potential vanilloid subfamily member 1, TRPV1, was the first member of a family of heat sensitive ion channels to be identified in mammals. Under normal physiological conditions, TRPV1 expressed in dorsal root ganglion neurons (DRG), is activated by thermal stimuli > 43°C. However, when tissues are damaged thermal allodynia/hyperalgesia occur due to modulation by inflammatory mediators released following the insult. Capsaicin directly activates TRPV1 and is used as a tool to study the properties of this receptor. Isolated DRG neurons are a mixed population of sensory neurones, some of which express TRPV1 ion channels, along with the G-protein coupled receptors for prostaglandins and bradykinin (BK). The aim of these experiments was to determine 1) which inflammatory mediator pathways converge on the TRPV1 ion channel using specific antibodies to co-localise TRPV1 with the EP4 receptor for PGE2, and the B2 receptor for BK, in tissue sections of rat DRG, and 2) the responses of isolated DRG neurons to capsaicin and their modulation by inflammatory mediators. All rats used in this study were killed under Schedule 1 of the Animals (Scientific Procedures) Act, 1986. Analysis of frozen tissue sections (n=12 sections from 3 rats) labelled with selective antibodies (Chopra et al, 2000) revealed that 21% of DRG neurons express all three proteins, EP4, B2, and TRPV1. To examine the sensitising effect of PGE2 on the TRPV1, adult rat DRG neurone cultures were prepared as previously described (Chopra et al, 2000). DRG neurons were loaded with fluo-4 and changes in the intracellular calcium concentration were monitored using an Olympus FV300 laser scanning confocal microscope. Capsaicin-evoked (80nM) calcium responses of cultured DRG neurons desensitised in 88.7% of capsaicin-sensitive neurons upon repeat application of the agonist. However, in the presence of 500nM PGE2 a significant sensitization of the capsaicin response was observed in 43.9% of these neurons (P<0.05, ANOVA) and in 31.7% of neurons that were initially capsaicin insensitive. Moreover, in presence of 100nM BK (preincubated with thapsigargin) 61% of capsaicin sensitive neurons and 14% of silent neurons were also sensitised by this agonist. However, preincubation of the DRG neurons with 3µM indomethacin (a non-selective cyclooxygenase inhibitors) decreased the proportion of capsaicin-sensitive neurons that were sensitised by bradykinin to 37%, and significantly decreased the magnitude of the capsaicin-evoked calcium responses from 2.87+/-0.21 a.u. to 1.93+/-0.11 a.u. (P<0.05, ANOVA) of the control value. These results suggest a role for cyclooxygenase enzyme and prostaglandins in the modulation of bradykinin-induced sensitization of DRG neurone responses to capsaicin.