Diabetes
Understanding why some diabetics feel no pain
By Pankaj, US correspondent
Dec 16, 2004, 18:01

Diabetes-associated nerve fiber damage, known as diabetic neuropathy, can result in a decreased ability of affected individuals to feel pain. Beginning with reduced sensation in the feet and legs, and in combination with poor circulation, the condition often results in the development of nonhealing ulcers. The molecular events that cause this loss of pain perception are poorly understood. In the December 15 issue of the Journal of Clinical Investigation, Peter Nawroth and colleagues from the University of Heidelberg report that levels of the RAGE receptor and its ligand, AGE, are increased at the sites of peripheral nerves in diabetic patients. AGE was shown to induce increased and sustained activation of NF-kappaB, which is closely associated with nerve dysfunction, and this could be partially reversed by blockade of the RAGE receptor.

Furthermore, the authors were able to partially reverse the loss of pain perception, associated with long-standing diabetic neuropathy, in mice treated with soluble RAGE, which is able to block the binding of AGE to the RAGE receptor. The data suggest that although RAGE has a substantial role in mechanisms leading to neuronal stress and sensory deficits in diabetes, it is certainly not the only factor. Although by revealing that the AGE-RAGE interaction impacts neuronal function, there is a strong case to support the development of AGE inhibitors for the treatment of human diabetic neuropathy.



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