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Diabetes is associated with numerous complications. One of the most debilitating microvascular sequelae is painful diabetic peripheral neuropathy (PDPN). PDPN results from a multi-faceted pathogenesis involving direct axonal degeneration; free radical mediated cellular apoptosis, and microvascular perfusion abnormalities. While tight glycemic control has been shown to modulate the history of this diabetic complication, practicing clinicians have access to numerous published practice recommendations for treatment. Of the frequently utilized medication classes, anticonvulsants, antidepressants, anesthetics, and the neuromodulators are perhaps the most widely understood. The gabapentinoids are considered by many as first line therapy. Others recommend tricyclic antidepressants firstline. The provider treating PDPN must consider the medication side effects and monitoring parameters, the co-morbid disease states, and the ultimate effects on diabetic control. Finally, the clinician must address patient expectations of treatment. Goals may include increased functionality, decreased pain and improved sleep. Here multiple treatment modalities and evidence-based guidelines are reviewed.

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