Potential therapeutic approaches to the treatment or prevention of diabetic neuropathy: evidence from experimental studies.

Recent investigations using experimental models of diabetes mellitus have emphasized the importance of impaired blood flow for the development of nerve dysfunction. Other observations suggest that this may also be the case for patients. A number of studies have revealed that several types of vasodilators can prevent or successfully treat early conduction abnormalities in diabetic rodents. These include alpha 1-adrenoreceptor antagonists, calcium channel blockers, agents that inhibit the renin-angiotensin system, and vasomodulator prostanoids. Other treatments applied to animal models, such as omega-6 essential fatty acids, aldose reductase inhibitors, aminoguanidine which prevents the formation of advanced glycation end-products, and anti-oxidants all appear to have vascular-related effects that lead to improvements in nerve conduction. These findings suggest that endothelial dysfunction and oxidative stress could be important factors in the aetiology of diabetic neuropathy. Studies have also focused on deficits in axon growth and regeneration, their relation to impaired neuronal synthesis and transport of growth-related chemicals, and neuronotrophic abnormalities. Taken together, the data give rise to the notion that an optimal therapeutic strategy could consist of improving the microenvironment of damaged nerve fibres by manipulating nerve blood flow while concurrently encouraging repair with trophic agents.