Diabetes is becoming a significant burden on global health care systems due to the onset of associated complications. A large proportion of diabetic patients develop neuropathy leading to chronic pain [1] as a result of glucose toxicity, which directly damages neurons. The transient receptor potential ankyrin 1 (TRPA1) channel has a fundamental role in the development of diabetic neuropathy resulting in pain and sensory neuronal loss in rodents [2]. We have demonstrated that vascular endothelial growth factor (VEGF) 165b has neuroprotective actions, and that systemic treatment of diabetic rats with the VEGF165b prevented development of diabetic neuropathy (enhanced nociception and loss of cutaneous nerve terminals) in vivo [3]. We therefore tested the hypothesis that TRPA1 activity in sensory neurons was altered by hyperglycaemia, and that VEGF165b could modify this. Immortalised embryonic dorsal root ganglion cells [4] were incubated in neurobasal medium for 48hrs and differentiated by 24hr incubation in 75μM forskolin. Cells were then incubated in experimental media for 24hrs (+ 75 μM forskolin) as follows; normal neurobasal media (control), neurobasal media + additional 30mM glucose (hyperglycaemia); neurobasal media + 30mM glucose + VEGF165b (2.5nM) or neurobasal media + 30mM mannitol (osmotic control). Cells were loaded with fluo4 for 1hr at 37oC, and agonist-induced increases in intracellular calcium measured in response to 100μM allyl isothiocyanate (AITC; TRPA1 agonist). Hyperglycaemia increased total AITC-induced calcium increase (0.92+0.068 fold change.s n=10; mean+SEM of area under curve) compared to control (0.43+0.20 fold change.s vs glucose n=10 p<0.01 one way ANOVA with post Bonferroni). No change was seen in the presence of 30mM mannitol (0.37+0.092 fold change.s). Treatment of cells with VEGF165b under hyperglycaemic conditions attenuated the response to AITC compared to hyperglycaemia alone (hyperglycaemia 0.92+0.068 fold change.s vs. hyperglycaemia + VEGF165b 0.33+0.16 fold change.s, p<0.05 n=4 Kruskal Wallis with Dunns multiple comparison). These data demonstrate that agonist-activation of TRPA1 is enhanced by hyperglycaemia in vitro, and that this can be attenuated by treatment with the growth factor isoform VEGF165b. TRPA1 has been shown to contribute to diabetic neuropathy (neuronal loss and pain). We propose that VEGF165b may attenuate the consequences of diabetic neuropathy including nerve terminal loss and pain, through inhibition of hyperglycaemic sensitisation of TRPA1.