As the RAGE agonist HMGB1 is increased in skin in diabetic rats when pain behaviour is altered (data herein, and Hulse et al., 2015), and RAGE expression is increased in sensory neurons (Zochodne, 2014), these peripheral actions of HMGB1 may be a contributory factor in the pain associated with glucose-induced neuronal damage and pain in diabetes. This evidence concerns the gene AGER and diabetes mellitus.