A new look at painful diabetic neuropathy.

The prevalence of diabetes mellitus and its chronic complications continue to increase alarmingly. Consequently, the massive expenditure on diabetic distal symmetrical polyneuropathy (DSPN) and its sequelae, will also likely rise. Up to 50% of patients with diabetes develop DSPN, and about 20% develop neuropathic pain (painful-DSPN). Painful-DSPN can cast a huge burden on sufferers' lives with increased rates of unemployment, mental health disorders and physical co-morbidities. Unfortunately, due to limited understanding of the mechanisms leading to painful-DSPN, current treatments remain inadequate. Recent studies examining the pathophysiology of painful-DSPN have identified maladaptive alterations at the level of both the peripheral and central nervous systems. Additionally, genetic studies have suggested that patients with variants of voltage gated sodium channels may be more at risk of developing neuropathic pain in the presence of a disease trigger such as diabetes. We review the recent advances in genetics, skin biopsy immunohistochemistry and neuro-imaging, which have the potential to further our understanding of the condition, and identify targets for new mechanism based therapies.