Painful Diabetic Neuropathy: Epidemiology, Natural History, Early Diagnosis, and Treatment Options


  • Disclosure Information: An earlier version of this article was written with the editorial assistance of IMPRINT Publication Science, which is supported by an unrestricted grant from GlaxoSmithKline. The authors received no honoraria and GSK were not privy to any review of the material before submission.

  • Dr. Backonja has received honoraria, consulting fees, or grant/research support from Endo Pharmaceuticals, GlaxoSmithKline, Johnson & Johnson, NeurogesX, Inc., Novartis Pharmaceuticals, Pfizer Inc., Purdue Pharma LP, Wyeth, and XenoPort. Dr. Malik has received honoraria or consulting fees from AstraZeneca Pharmaceuticals, Takeda Pharmaceuticals, and Pharma Inc. and grant/research support from AstraZeneca. Dr. Veves is a member of the Advisory Panel of GlaxoSmithKline.

Aristidis Veves, MD, Microcirculation Laboratory, Palmer 317, BIDMC/West, One Deaconess Road, Boston, MA 02215, USA. Tel: 617 632 7075; Fax: 617 632 7090; E-mail:


Objective.  To facilitate the clinician’s understanding of the basis and treatment of painful diabetic neuropathy (PDN).

Background.  PDN is one of several clinical syndromes in patients with diabetic peripheral neuropathy (DPN) and presents a major challenge for optimal management.

Methods.  A systematic review of the literature was undertaken for articles specific to PDN, using Medline databases between 1966 and 2007.

Results.  The epidemiology of PDN has not been well established and on the basis of available data the prevalence of pain is 10% to 20% in patients with diabetes and from 40% to 50% in those with diabetic neuropathy. It has a significant impact on the quality of life and health care costs. Pathophysiologic mechanisms underlying PDN are similar to other neuropathic pain disorders and are broadly characterized as peripheral and central sensitization. The natural course of PDN is variable, with many patients experiencing spontaneous improvement and resolution of pain. Hyperglycemia-induced pathways result in nerve dysfunction and damage, which lead to hyperexcitable peripheral and central pathways of pain. Glycemic control may prevent or partially reverse DPN and modulate PDN. Quantifying neuropathic pain is difficult, especially for clinical trials, although this has improved recently with the development of neuropathic pain-specific tools, such as the Neuropathic Pain Questionnaire and the Neuropathic Pain Symptom Inventory. Current therapeutic options are limited to symptomatic treatment and are similar to other types of neuropathic pain.

Conclusions.  A better understanding of the peripheral and central mechanisms resulting in PDN is likely to promote the development of more targeted and effective treatment.