Essential Insights On Managing Symptomatic Diabetic Neuropathy

Stephanie Wu, DPM, MS

Given the common prevalence and debilitating effects of neuropathic pain, it is important to have a strong understanding of effective treatment options. Accordingly, this author reviews the literature on currently available modalities as well as emerging therapies.

   Chronic neuropathic pain is a significant public health issue, which is often associated with negative physical, psychological and social sequelae.1-3 Pain is considered the third most common healthcare problem and it disables more individuals than heart disease and cancer combined.1

   In particular, neuropathic pain includes nerve-injured neuropathy, diabetic neuropathy, chronic inflammatory pain, complex regional pain syndrome and postherpetic neuralgia. Pain is often characterized by a tactile allodynia and hyperalgesia.2,4 Pain perception and interpretation is further complicated by cognitive, affective and behavioral factors. It is often associated with diminished physical and emotional functioning, as well as affective symptoms.5

   Painful or symptomatic neuropathy is a common and debilitating complication of diabetes mellitus. It is one of the most commonly encountered neuropathic pain syndromes in clinical practice.2,6 Research has found that patients with symptomatic diabetic peripheral neuropathy have a significantly higher prevalence of comorbidities. This includes twice as many limb infections, a 2.5-fold higher likelihood of hospital admissions and nearly tenfold greater limb amputations.7

   Further, patients with painful diabetic peripheral neuropathy (DPN) have had consistently higher healthcare service utilization and costs across all categories of care.7 One study found that peripheral neuropathy, both symptomatic and non-symptomatic, was nearly twice as prevalent in patients with type 2 diabetes (50.8 percent) versus those with type 1 diabetes (25.6 percent).8

   There are three broad types of neuropathy (sensory, motor and autonomic) associated with diabetes. Sensory neuropathy is the most prevalent of the three and is often simply referred to as DPN. Patients typically experience diverse sensory symptoms including dysesthesias in the feet that may often be accompanied by sleep disturbances.6,9 Small fiber neuropathy is increasingly being recognized as a major cause of painful burning sensations in the feet.10 Although patients generally retain their strength throughout the course of the disease, the pain and paresthesias are often disabling and impose subsequent negative impact on the patients’ health-related quality of life.10

   Diabetes is the most common identifiable cause of small fiber neuropathy. Impaired oral glucose tolerance and individual components of this metabolic syndrome are often associated with the rate of progression. Recent research has shown that in addition to poor glucose control, independent risk factors for incident DPN include traditional cardiovascular risk factors for macrovascular disease. Other factors include age, diabetes duration, nephropathy, obesity, low high-density lipoprotein (HDL) cholesterol, high triglyceride levels and the female gender.8,11

   To date, there is still no comprehensive understanding of the underlying biologic processes responsible for diabetic neuropathic pain. However, studies have demonstrated differences in sural nerve epineurial blood flow, foot skin microcirculation, intraepidermal nerve fiber density and thalamic magnetic resonance spectroscopy between individuals with symptomatic versus painless neuropathy.6,11

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