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Pain Management of Diabetic Neuropathy

A lack of standardization in the diagnosis of diabetic neuropathy and the challenge of symptom management contribute to the lack of a gold standard of treatment for this condition.
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Diabetic neuropathy (DN) is estimated to occur in 50% of patients with long-standing type 1 and type 2 diabetes mellitus (DM).1 It is one of the major microvascular complications associated with DM that can cause considerable morbidity and mortality.2 DN presents with a heterogeneous spectrum of clinical and subclinical syndromes.3 It can manifest as mononeuropathy, polyneuropathy, and/or autonomic neuropathy.1 The major complication of somatic neuropathy is foot ulceration, which often leads to gangrene and limb loss. In fact, DN causes 50% to 75% of all ulcerations and nontrauma amputations in the United States4 and causes more hospitalizations than all other diabetic complications combined.3

High Risk of Complications
Risk for chronic complications in DM correlates with the duration of hyperglycemia. Therefore, undetected DM may cause extensive damage to the nervous system. There is a subtle distinction between the deterioration of type 1 and type 2 DM. In type 1 DM, nerve function rapidly deteriorates soon after its onset. By contrast, in type 2 DM, patients often have a long, asymptomatic period of hyperglycemia; consequently, they have subclinical or clinical neuropathic complications at the time of diagnosis.1 In fact, studies have show nerve pathology is present very early in type 2 DM, and nerve conduction velocities (NCVs) are delayed even before diagnosis.5 In addition to the duration of the disease, patient age also has a direct association with the progression of neuropathy.3 Other risk factors for DN include height, hypertension, hypercholesterolemia, cigarette smoking, and alcohol consumption.3

The epidemiology and disease course of DN remain poorly defined, in part because of variable diagnostic criteria, the failure of many physicians to identify and diagnose the disease, and a lack of standardized methodologies for the evaluation of these patients.Of the estimated 50% of patients with diabetes who have DN, 2.7 million have painful neuropathy.7 During the course of the disease, however, the pain subsides and eventually disappears, leaving behind a persistent sensory deficit.8 Because the pain of acute DN may resolve within the first year, analgesics may be discontinued as progressive neuronal damage from DM occurs. Chronic, painful DN is difficult to treat but may respond to a variety of pharmacologic agents. Referral to a pain management center may be necessary if pain is refractory to treatment.1

Diagnostic Difficulties
DN remains underdiagnosed. In the GOAL A1c (Glycemic Optimization with Algorithms and Labs at Point of Care) study, which assessed how often neuropathy is accurately diagnosed, the researchers found that the presence of mild neuropathy was accurately diagnosed in only one-third of all cases.9 Severe neuropathy was accurately diagnosed in 75% of patients evaluated. Evidently, there is a need for elucidating the science of correctly diagnosing DN in a timely manner so that physicians can employ preventive as well as therapeutic techniques.3

A thorough patient history is a prerequisite to making a diagnosis of DN.3 Conducting the assessment solely by the identification of neuropathic symptoms is not useful or accurate in the diagnosis of DN. Symptoms of painful neuropathy should be evaluated with extra caution, because they can arise from other nonspecific causes. It is essential to thoroughly examine and assess both the central and peripheral nervous systems, with emphasis on the nerves most likely to be affected by diabetes.3

The Rochester Diabetic Neuropathy Study, an assessment of tests and criteria for diagnosis and stage severity, proposed two abnormal evaluations (from among neuropathic symptoms, neuropathic deficits, nerve conduction velocity [NCV] tests, quantitative sensory tests, and quantitative autonomic function tests [QAFT]), with one of the two being abnormality of nerve conduction or QAFT. (Decreased heart rate response to deep breathing or the Valsalva maneuver was found to be the most sensitive and objective.)10

Treatment of DN focuses on preventing progression of neuropathy, reducing symptoms, and preventing complications of insensate extremities.3 Successful management of these syndromes must be directed to the individual pathogenic processes.3 Treatment of DN can be broken down into protective and symptomatic.11

Glycemic control is a crucial factor in the management and prevention of neuropathy. The Diabetes Control and Complications Research Group demonstrated statistically significant effects of intensive insulin therapy on the prevention of neuropathy.12 Tight control of serum glucose can improve symptoms over short time periods, although this has been seen only in uncontrolled trials.13 A simple rule demonstrated that a 1% fall in HbA1c ameliorates conduction velocity by about 1.3 m per second.14 The United Kingdom Prospective Diabetes Study showed that management of glucose levels with intensive treatment was associated with improvement in vibration perception.15 The Steno trial was a stepwise, progressive study that involved treatment of type 2 diabetic patients with angiotensin-converting enzyme inhibitors, Ca2+ channel antagonists, hypoglycemic agents, aspirin, hypolipidemic agents, and antioxidants. The evidence further substantiates the multifactorial nature of neuropathy and the significance of addressing the multiple metabolic abnormalities linked with diabetes.16

The most challenging facet of DN is the treatment and management of symptoms. The pain from DN can be excruciating and debilitating. Pain typically involves the lower extremities and commonly manifests at rest and is exacerbated at night. Painful DN can occur acutely (lasting <12 months) and chronically. Diabetic polyradiculopathy is a syndrome that presents with severe disabling pain in the distribution of one or more nerve roots; it may be associated with motor weakness. Fortunately, diabetic polyradiculopathies are usually self-limited and improve over 6 to 12 months. Management of painful neuropathy usually requires treatment with antidepressants, anticonvulsants, analgesics, and other pharmacotherapy (see Table, page 20). However, before initiating pharmacotherapy, patients should be informed that 100% symptom resolution usually is not feasible regardless of the treatment plan implemented.17

Last updated on: June 12, 2012
First published on: April 1, 2012