Rats with experimental diabetes show changes in prenuclear signals that might impact on neuronal transcription factors; these in turn may be responsible for the phenotype switches characteristic of diabetic neuropathies. This study was designed to examine the effect of streptozotocin-diabetes of 12 weeks' duration on the activation of three transcription factors known to affect neuronal phenotype in dorsal root ganglia (DRG). Pooled L4 and L5 were subject to gel-shift analysis to measure binding to consensus oligonucleotides. This revealed significant reduction in activation of CREB and NFkappaB in DRG from diabetic rats, but no effect on AP-1. The CREB change may be secondary to target tissue NGF depletion, and the reduced NFkappaB indicates impaired capacity to withstand neurotrophic defects. Thus, these changes my underlie consequences of impaired neurotrophic regulation of phenotype reported in other studies in diabetic rats.