FROM THE CLINICAL KNOWLEDGE CENTER
Emerging Issues in Neuropathic Pain

by Lisa Brauer, PhD

August is National Pain Awareness month, and in this issue of Clinical Compass™ we will address a particularly chronic and difficult to treat problem - neuropathic pain.

Neuropathic pain is a significant public health problem, affecting an estimated 75-150 million people in the United States alone(1). It is associated with substantial disability in up to 30% of patients and has a considerable negative impact on quality of life. Neuropathic pain carries significant cost in terms of use of medical resources, lost work, and work productivity(2).

Patients with neuropathic pain commonly experience comorbid medical illnesses and take a number of medications, which can complicate treatment(3), as well as depression, anxiety, and sleep disturbances, which can exacerbate symptoms and lead to worse outcome(4).

Neuropathic pain has numerous and diverse etiologies including diabetes, cancer, some medications, and neurological disorders, and it has a variety of unique symptoms. Patients describe the pain as burning, electricity, tingling, numbness, and extreme cold. Perhaps in part because of its varied pathogenesis and presentation, neuropathic pain is difficult to treat. As a rule, only 30-50% of patients treated with first-line therapies achieve at least a 50% reduction in pain. Nevertheless, it has been suggested that a 30% reduction in pain on a 0 (no pain) to 10 (worst pain) scale is clinically significant(3).

Polypharmacy is generally the standard of care in the treatment of neuropathic pain - there is no one “gold standard” medication used to manage patients(2), and it is generally not possible to predict which agents will be effective for a given patient. Pharmacologic therapies are not cures, and they must be used in the context of a more comprehensive management approach that includes education, support, reassurance, and nonpharmacologic interventions.

Evidence-based treatment recommendations for neuropathic pain have been published based on the results of an increasing number of clinical trials in this area(3). In addition, two medications have received FDA approval for the management of neuropathic pain in the last few years(5). Taken together, medical literature suggests that the first line treatments for neuropathic pain include the anticonvulsants pregabalin and gabapentin, the SNRI duloxetine, the tricyclic antidepressants, the opioid analgesics, and tramadol hydrochloride. Of these medications, carbamazepine, gabapentin, pregbalin, duloxetine, and the 5% lidocaine patch are FDA-approved for the treatment of neuropathic pain of varying etiologies.

Each class of medication has advantages and risks that must be weighed when choosing a course of treatment. For instance, several clinical trials have shown that the newest additions to the treatment options, pregabalin and duloxetine, are effective, safe, and well-tolerated in patients with neuropathic pain, and may confer additional benefit on mood symptoms that often occur in this population(6,7). Both also have been shown to significantly improve quality of life in patients with neuropathic pain. While pregabalin can reduce pain-related sleep disturbances, duloxetine may have activating effects and may be more appropriate for patients without sleep concerns(6,7). Duloxetine, on the other hand, owing to its known efficacy against depression, may be more appropriate for patients with neuropathic pain who have more significant mood cormorbidities(7). Pregabalin is associated with some abuse potential so use should be carefully monitored by physicians(6). Similarly, opioid analgesics may pose risk of abuse in patients with histories of substance abuse(3). Care also must be taken when using this class of drugs in elderly patients because they may cause cognitive and/or mobility problems that can lead to fractures(3). Tramadol may cause seizures in patients with a history of seizures or who are receiving other drugs that increase this risk(3). Serotonin syndrome is a risk that must be considered when prescribing tramadol in patients on other drugs that elevate serotonin(3).

In summary, neuropathic pain is a prevalent disorder that is often refractory to treatment. As more is known about the pathophysiology and varying clinical presentations of neuropathic pain, greater advances can be made in terms of medical management. Recent developments in the pharmacologic management of neuropathic pain may pave the way toward better symptom control but must be used as part of a more comprehensive pain management strategy. Moreover, each medication must be weighed in terms of risk and benefit for particular patients, and several options may need to be tried before pain can be adequately managed. Given the significant association of neuropathic pain with medical and psychiatric comorbidity, reduced quality of life, disability, and direct and indirect costs, there is an urgent need for both development of new treatments and education efforts on how to best individualize treatment plans based on current available options.

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