Blockade of HMGB1–RAGE-mediated neuronal sensitisation by rhVEGF-A165b in vitro supports our hypothesis that alteration of VEGF-A isoforms, for example by treatment with rhVEGF-A165b or an agent that alters VEGF-A splicing to favour VEGF-A165b may be an effective treatment for diabetic neuropathy. This evidence concerns the gene AGER and diabetic neuropathy.