The non-selective cation channel vanilloid receptor 1 (TRPV1) is expressed by a sub-population of primary sensory neurones. It is activated either by direct interactions with activators, such as capsaicin or heat <43°C, or indirect actions by ligands acting on other receptors, such as nerve growth factor on the tyrosine kinase A (trkA) receptor. This latter type of activation is mediated by post-translational changes of TRPV1. Recent data shows that TRPV1 is often co-expressed with the insulin receptor in sensory ganglion neurones and that trkA and the insulin receptor have common components in their signalling pathways, suggesting that insulin may activate TRPV1 indirectly. Therefore, we studied the effects of insulin on membrane currents in cultured primary sensory neurones. Neuronal cultures were prepared from dorsal root ganglia of terminally anaesthetized (isoflurane) Wistar rats (n=7), and kept in F-12 culture medium supplemented with 50ng/ml NGF. Capsaicin (500nM)- and insulin (10μM)-induced whole cell currents were recorded at E_m=-60mV at room temperature from neurones of 3-6 day-old cultures. The composition of the bath and pipette solutions were (mM): NaCl 130, KCl 5, CaCl₂ 2, MgCl₂ 2, Hepes 10, glucose 10 (pH 7.4), and KCl 130, NaCl 5, MgCl₂ 2, Hepes 10 (pH 7.4), respectively. Data are expressed as mean±S.E.M., statistical analysis was performed by Student’s t test, p<0.05. Thirty of the 94 capsaicin-sensitve, but non of the capsaicin-insensitve cells responded to insulin. The peak amplitude of the insulin-evoked current was 227±52pA. The activation kinetics of the insulin-induced currents was slower than that of the capsaicin-evoked responses (time to peak: 12.58±0.78s vs. 18.76±1.74s). The capsaicin-induced current was significantly greater in insulin-responsive (614±21pA) than in the insulin non-responsive cells (278±5pA, p=0.022). While capsaicin-evoked currents desensitised following repeated administration of capsaicin, there was no apparent desensitisation in the insulin-induced currents. The competitive TRPV1 antagonist, capsazepine (5μM) strongly reduced the capsaicin-induced but not the insulin-induced currents. These findings show that insulin induces membrane currents in a proportion of capsaicin-sensitive cultured primary sensory neurones, though, at present it is not clear whether the insulin-induced responses are mediated by TRPV1. Nevertheless, our data suggest that insulin might significantly influence the functions of a proportion of primary nociceptors.