Pathophysiology and Treatment of Painful Diabetic Neuropathy of the Lower Extremity

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Symptomatic peripheral neuropathy is the most common complication of diabetes mellitus, affecting up to 62% of Americans with diabetes.


We reviewed the literature using the National Library of Medicine's MEDLINE search service. In total, we reviewed 54 articles.


Hyperglycemia leads to increased activity in the polyol pathway in nerve cells; this ultimately results in abnormal nerve function. Numerous pharmacologic agents have been used to treat symptomatic peripheral neuropathy, but all of these drugs can be associated with adverse side effects. Recent work has indicated that subsensoiy electrical stimulation may be preferred to pharmacotherapy, since it is equally effective and has a more favorable safety profile.


Although the pathophysiology of diabetic neuropathy is well understood, treatment of the symptoms associated with this condition can be challenging. Additional research is needed to reveal a safe and effective treatment for this debilitating sequela of diabetes mellitus.

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