The RAGE pathway: activation and perpetuation in the pathogenesis of diabetic neuropathy.

The molecular mechanisms underlying loss of pain perception in diabetic neuropathy are poorly understood. Experimental diabetic neuropathy models recently provided evidence that engagement of the receptor for advanced glycation end products (RAGE) and RAGE-dependent sustained activation of the proinflammatory transcription factor nuclear factor kappa B might significantly contribute to reduced nociception. Most importantly, diabetes-induced loss of pain perception is largely prevented in RAGE-deficient mice compared to RAGE-bearing wild-type mice. Identifying RAGE-dependent inflammation as one pathomechanism underlying neuronal dysfunction might provide the basis for new therapeutic approaches.