Diabetic Peripheral Neuropathic Pain

Diabetes mellitus (DM) has been a significant public health problem for many years. However, the number of cases is continuing to grow at such an alarming rate that some have suggested we are facing or are already experiencing a "diabetes epidemic." Since peripheral neuropathy is commonly associated with DM, occurring in at least 50% of patients,¹ there will no doubt be a rise in this problem as well. Although diabetic neuropathies can present in a variety of forms, including the loss of sensory and motor functions, pain is one of the more common symptoms. A recent study reported that neuropathy is a problem so commonly associated with DM that all patients with symptoms of peripheral neuropathies, including pain, should receive a 2-hour oral glucose tolerance test to rule out undetected DM.²

Diabetic peripheral neuropathic pain (DPNP) is most commonly described as a burning or electric shock-like sensation in the feet and lower extremities, although the hands can also be affected. Patients may also experience allodynia, in which normally nonpainful stimuli induce pain, or hyperalgesia (in which there is an increase in response to a painful stimuli). Curiously, even when patients are experiencing pain, they may complain of numbness over the affected area. Patients usually report that placing weight on their feet exacerbates the pain. DPNP frequently worsens at night, which can cause or increase sleep problems. Interestingly, insomnia has been reported to be associated with abnormal glucose tolerance test results and may precipitate DM.³

Although DPNP appears to be related to pathologic changes in the peripheral nerves, why some patients with peripheral neuropathy develop pain while others do not remains uncertain. Better glucose control appears to reduce the overall risk of developing diabetic peripheral neuropathy, but it is still unclear whether it specifically decreases the incidence of DPNP.

Neuropathic pain, including DPNP, is among the most difficult forms of pain to treat. Many medications have been tried and most have either been found to be ineffective or to have side effects that drastically limit their use. However, a number of medications have been consistently found to provide relief for DPNP. Two recent papers that examined the literature on neuropathic pain⁴ and, in DPNP specifically,⁵ provided guidance in choosing the most effective pharmacologic options.

Finnerup and colleagues⁴ recommended beginning treatment with a lidocaine(Drug information on lidocaine) patch (Lidoderm) with 5% lidocaine if the pain is localized. Although this medication is FDA-approved only for the treatment of postherpetic neuralgia (PHN) pain, there is research indicating that it is effective for DPNP also.⁶ A significant advantage of this medication is the limited potential for side effects because it is a topical medication.

The 2 review papers were essentially in agreement with regard to choosing oral medications for pain. Both found that the literature most strongly supported the use of the tricyclic antidepressants (TCAs), pregabalin(Drug information on pregabalin) (Lyrica) and duloxetine(Drug information on duloxetine) (Cymbalta) (the only 2 medications that are FDA-approved for the management of DPNP), and controlled-release oxycodone(Drug information on oxycodone) (OxyContin, others). The major factors to consider when choosing which medication to try first are the associated side effects and the presence of comorbid medical and psychiatric conditions.

Of all of the medications, the TCAs probably have been studied the most and have consistently demonstrated marked analgesia for neuropathic pain. They have the additional benefits of offering relief for depression, which is experienced by many patients with DPNP,⁷ and ameliorating insomnia through their sedative effects. Obviously, the drawback to their use is the side-effect profile, which includes anticholinergic and cardiotoxic effects.