Treatment Options for Neuropathic Pain

Phoenix—When Mark Wallace, MD, began his medical career in 1995, the FDA had approved only a single drug for neuropathic pain. Now his choices are much broader, although the approval of several medications in recent years has made it sometimes difficult to determine how to best treat patients.

Dr. Wallace, professor of clinical anesthesiology at the University of California, San Diego, addressed the numerous options for neuropathic pain at the AAPM meeting.

Pain can be classified into 4 categories, according to Dr. Wallace: (1) nociceptive (transient pain in response to a noxious stimulus); (2) inflammatory (spontaneous pain and hypersensitivity to pain in response to tissue damage and inflammation); (3) functional (hypersensitivity to pain resulting from abnormal central processing of normal input); and (4) neuropathic (spontaneous pain and hypersensitivity to pain in association with damage to or lesion of the nervous system).

He added that neuropathic pain can be difficult to diagnose because ≥1 mechanism of action is likely involved and it may result from abnormal peripheral nerve function and neural processing of impulses. When managing pain, patients may need to take numerous medications such as topicals, anticonvulsants, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and opioids.

To determine the presence or severity of neuropathic pain, Dr. Wallace said clinicians must understand a patient’s symptoms, the onset of the disease, and etiologic factors such as whether the patient has diabetes, drinks alcohol, has vitamin deficiencies, or suffers from trauma or structural lesions. Neuropathic pain can be spontaneous (continuous or intermittent) or stimulus-evoked, and patients can have an increased or decreased response to painful or nonpainful stimulus, increased or decreased sensitivity to stimulation, and abnormal or unpleasant sensations.

When trying to determine if a person has neuropathic pain, there are several tools to use, Dr. Wallace said, including the Leeds Assessment of Neuropathic Symptoms and Signs, the Neuropathic Pain Questionnaire (NPQ), and the Neuropathic Pain Diagnostic Questionnaire. To measure the characteristics of neuropathic pain, Dr. Wallace suggested the NPQ, Neuropathic Pain Scale, and the Neuropathic Pain Symptom Inventory.

A neurologic examination may consist of testing patient’s pain with a touch or pin prick; taking body temperature; measuring muscle strength, coordination, and gait; and performing diagnostic studies such as drawing blood or obtaining an x-ray, a computed tomography scan, or a magnetic resonance imaging exam.

Dr. Wallace emphasized that clinicians should follow what he refers to as the “pain treatment continuum,” focusing on the therapeutic options that are as least invasive as possible to treat the pain. For example, they should begin with psychological or physical approaches first and then progress to topical medications, systemic medications, and interventional techniques when necessary.

The FDA-approved treatments for neuropathic pain are capsaicin patch 8% (for postherpetic neuralgia), duloxetine (for peripheral diabetic neuropathy, fibromyalgia, and chronic musculoskeletal pain), gabapentin (for postherpetic neuralgia), lidocaine patch 5% (for postherpetic neuralgia), milnacipran (for fibromyalgia), pregabalin (for peripheral diabetic neuropathy, postherpetic neuralgia, and fibromyalgia), and carbamazepine (for trigeminal neuralgia). Of the neuropathic pain disorders, diabetic neuropathy and postherpetic neuralgia are the most common, and most randomized controlled trials involve either of those diseases, according to Dr. Wallace.

Dr. Wallace provided an overview of a few of the medications. Patients apply up to 3 lidocaine patches once daily over the site where pain is located. The efficacy of lidocaine was demonstrated in 3 randomized controlled trials of patients with postherpetic neuralgia. In 2007, a meta-analysis found that topical lidocaine had greater pain relief compared with placebo (P=.003), and the incidence of adverse skin reactions were similar between the groups.

In the trials, the most common side effect associated with lidocaine was application-site sensitivity, and Dr. Wallace noted that drug interactions and systemic side effects were unlikely.

Patients who are prescribed the capsaicin patch are advised to apply up to 4 patches to the painful skin area for 60 minutes. Dr. Wallace said patients should apply the treatment only once every 3 months until the pain disappears.

One study found that 44% of patients who used the capsaicin patch achieved a ≥30% reduction in Numeric Pain Rating Scale (NPRS) score from baseline compared with 33% of patients in the control group (P=.0487). In another study, 47% of patients in the capsaicin group had a ≥30% reduction on the NPRS compared with 35% in the control group (P=.0212). The most common side effects associated with capsaicin were application site erythema and application site pain.

The typical daily dose for gabapentin is 3600 mg taken 3 or 4 times per day. A study found that patients taking gabapentin for postherpetic neuralgia were significantly more likely to have improvement in pain compared with patients taking placebo (P<.001).

The efficacy of pregabalin was determined in 6 trials, with reductions in pain found within a week of treatment. In 1 study, patients with postherpetic neuralgia or pain diabetic peripheral neuropathy who took 75 mg, 300 mg, or 600 mg of pregabalin daily had a significant pain reduction from baseline compared with those who received placebo.

Dr. Wallace also mentioned randomized controlled trials and meta-analyses have revealed that tricyclic antidepressants (such as amitriptyline, nortriptyline, and desipramine) are beneficial in treating postherpetic neuralgia and diabetic neuropathy. Although antidepressants are not approved to treat neuropathic pain disorders, they have led to improvements in insomnia, anxiety, and depression, according to Dr. Wallace.

In a randomized, double-blind crossover trial, there was no difference in efficacy in patients who took nortriptyline compared with amitriptyline to treat postherpetic neuralgia, although intolerable side effects were more common in the amitriptyline group. Dr. Wallace said patients should take the drug that has the fewest side effects.

Patients taking antidepressants have had adverse events such as blurred vision, cognitive changes, constipation, dry mouth, orthotastic hypotension, sedation, sexual dysfunction, tachycardia, and urinary retention. The most adverse events were found in patients who took amitriptyline, while those who took desipramine had the fewest adverse events.

Opioids are another option and play an important role in treating chronic pain, according to Dr. Wallace. However, he said clinicians should be careful in prescribing opioids and make sure to monitor for adverse effects or aberrant behaviors. Some people can become physically dependent on opioids and experience withdrawal if the drug is discontinued or the dose is reduced. Others may become addicted to opioids and compulsively use the drugs even if they are being harmed.