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4 Articles in this Series
Diabetes and Pain
Mindfulness Meditation
Pain and Autism: How to Better Treat a Pain Patient with Autism
Postherpetic Neuralgia: Effective PHN Prevention in the Elderly

Diabetes and Pain

For the first time, PAINWeek had a special section on the treatment of diabetes and pain. This educational tract covered peripheral artery disease (PAD), gastrointestinal pain, peripheral neuropathy, and musculoskeletal complications of diabetes.

Setting the stage was a presentation by Michael M. Bottros, MD, faculty in the department of anesthesiology and pain medicine and director of the acute pain service at Washington University School of Medicine, St. Louis, Missouri, on how to manage and even prevent progression of PAD in patients with diabetes. According to Dr. Bottros, the prevalence of PAD is higher in patients with diabetes, and diabetic patients with PAD have a 3- to 4-fold increased mortality compared to non-diabetics. The 5-year mortality in diabetic patients with crucial limb ischemia is 30%, he noted. 1

The coexistence of significant neuropathy and arterial calcifications are primary determinants for underdiagnosing PAD in patients with diabetes. In fact, PAD may be asymptomatic until it reaches an advanced stage in diabetic patients, noted Dr. Bottros. Diabetic patients who have decreased pain perception due to peripheral neuropathy may delay recognition of PAD. Ankle-brachial index measurement is the most accurate noninvasive diagnostic method, whereas foot examinations correlate poorly with a diagnosis of PAD, he noted.

Aggressive management of PAD early in the course of the disease can help prevent the development of later complications. Known risk factors for the development of PAD, he said, include smoking, older age, hypertension, and poor glycemic control, while high levels of the good cholesterol (high density lipoproteins) and apolipoprotein A-1 exert protective effects. Therefore, physicians need to be proactive in their management of these patients, including encouraging patients to quit smoking (smoking cessation may halt progression of disease), and follow a proper diet and exercise regimen, which will increase cardiovascular fitness, oxidative enzyme activities, nitrous oxide production, and insulin sensitivity.

Aggressive medical management includes improvement of insulin resistance, dyslipidemia, and hypertension. Dr. Bottros cited one study in which the statin simvastatin was found to decreased morbidity and mortality by 25%.1 For patients with hypertension, it has been shown that tight control of blood pressure (<120/80) can decrease mortality by 25%.2 Pharmaceutical management includes the use of antiplatelet therapy, such as aspirin or clopidogrel (Plavix) for those patients sensitive to aspirin, he reported. A study of aspirin (75 mg) combined with dipyridamole resulted in the least progression of PAD compared with aspirin alone or placebo.1

For patients with pain associated with intermittent claudication, Dr. Bottros noted that there are two FDA-approved medications cilostazol (Pletal) and pentoxifylline. Cilostazol, which induces vasodilation by inhibiting calcium-induced contractions of smooth muscle cells, increased pain-free walking distance and quality of life, noted Dr. Bottros. It is contraindicated, however, in patients with congestive heart failure and severe hepatic or renal impairment. Pentoxifylline has been shown to benefit patients with severe claudication symptoms and those in whom exercise and/or cilostazol is not effective or is contraindicated.

Dr. Bottros also discussed novel approaches to increase blood flow to ischemic tissues, such as the use of vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor, and nerve growth factor. These can be given either through a topical administration or incorporated into genes encoding angiogenic growth factors. These may be indicated for the management of patients who are not candidates for revascularization surgery. He concluded with a discussion regarding the use of spinal cord stimulation. A meta-analysis showed that spinal cord stimulation could decrease amputation rates in 1 out of 8 patients by improving microcirculation.3 Even in those patients who proceeded with an amputation reported less pain and opioid consumption when using spinal cord stimulation.


  1. Jude EB, Eleftheriadou I, Tentolouris N. Peripheral arterial disease in diabetes—a review. Diabet Med. 2010;27(1)4-14.
  2. Heart Outcomes Prevention Evaluation Study Investigators.  Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet. 2000;355(9200):253-259.
  3. Ubbink DT, Vermeulen H, Spincemaille HJJ, et al. Systematic review and meta-analysis of controlled trials assessing spinal cord stimulation for inoperable critical leg ischemia. Br J Surg. 2004;91(8):948-955.
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