Insights into the pathogenesis and treatment of painful diabetic neuropathy.

Painful diabetic distal symmetrical polyneuropathy (painful DPN) is a puzzle with two important missing pieces: Firstly we still do not understand why only some patients with neuropathy experience painful symptoms; Secondly we still do not have a complete understanding of how nociception generated in the peripheral nervous system is processed by the central nervous system (CNS). Available treatments offer only symptom relief and there is currently no effective treatment based on arresting or reversing the progression of disease. Therefore the management of painful DPN remains less than optimal because the complex pathophysiology of nociception and pain perception in health and disease is incompletely understood. Studies of the peripheral nervous system are investigating the molecular processes involved in signal transduction that have the potential to be interrupted or modified to ease pain. Magnetic resonance imaging techniques are helping to elucidate central pain processing pathways and describe the translation of nociception to pain. Combining the knowledge from these two streams of enquiry we will soon be able to predict accurately who will develop painful DPN, how we can halt or reverse the condition, or who will respond to symptomatic treatments. Future developments in the treatment of painful DPN will be underpinned by decoding the peripheral and central mechanisms of pain. Research is focusing on these areas of enquiry in the hope that answers will lead to effective treatments to alleviate pain and reverse pathology for those suffering from painful DPN.