New recommendations help limit neuropathic pain

A glance at the meticulously outlined pathway that a stimulus must follow before it finally produces the sensation of pain will show that researchers have done their homework when it comes to understanding the underlying mechanisms of neuropathic pain. But despite this wealth of valuable information, safe and effective treatment of pain still poses a challenge to healthcare providers. Diverse side effects, drug interactions, and long periods of dosage titrations are just the tip of the iceberg.

An article in the November 2003 issue of Archives of Neurology presented evidence-based treatment recommendations for the pharmacological management of chronic neuropathic pain. The faculty of the Fourth International Conference on the Mechanisms and Treatment of Neuropathic Pain contributed as authors.

"Neuropathic pain is defined as pain caused by a lesion or dysfunction to the peripheral or central nervous system," stated lead author Robert H. Dworkin, Ph.D., department of anesthesiology, University of Rochester, in New York State. "If not treated, pain can have significant physical, psychological, and financial consequences," he said.

Based on positive results from multiple randomized controlled trials, the authors made recommendations for first-line pharmacological agents, including a 5% lidocaine patch, opioid analgesics, gabapentin, tramadol, and tricyclic antidepressants (TCAs).

According to the guidelines, the safety and efficacy of gabapentin in the treatment of chronic neuropathic pain originating from various conditions has been evaluated in multiple published clinical trials. Given at dosages up to 3600 mg/day over a four-week titration period, the anticonvulsant significantly reduced postherpetic neuralgia pain (PHN) when compared with placebo. While the authors recommend caution in treating elderly patients with gabapentin, since it may cause or exacerbate gait problems and cognitive impairment, its lack of drug interactions distinguishes it from other oral medications used to treat neuropathic pain.

Jorge Parrales, R.Ph., at Pharmacy Value in Guttenburg, N.J., emphasized that since the benefits of the drug are not immediate, he advises his patients to stay on their medication through the titration period. "The exciting aspect is that there are a variety of therapeutic options highlighted in this recently published article," he said. One might be old-time lidocaine dressed in a topical 5% patch. Lidocaine provides clinically meaningful pain relief to patients with PHN and allodynia (pain in response to a normally nonnoxious stimulus).

The idea of applying a topical lidocaine solution came from a pharmacist in desperate search for relief for his wife's painful and debilitating PHN. The R.Ph. initially applied a topical lidocaine solution to the affected area of his wife's back and then covered it with plastic wrap. His treatment eventually evolved into Lidoderm (lidocaine patch 5%, Endo Pharmaceuticals). The FDA-approved dosage for PHN is up to three patches applied to intact skin for up to 12 hours within a 24-hour period. Unlike oral agents such as gabapentin and TCAs, the 5% lidocaine patch requires no dose titration.

The manufacturer of the patch recommends caution in patients with severe hepatic disease or in patients receiving oral class-1 antiarrhythmic drugs, such as mexiletine and tocainide.

"While the evidence for considering opioid analgesics as a first-line treatment option for neuropathic pain is indicated in the Archives article, benefits of this medication class come with a price," noted Parrales. According to findings of a clinical trial published in the New England Journal of Medicine in March 2003, 27% of patients receiving oral opioid therapy for chronic neuropathic pain withdrew from the study—the majority because of physical or psychological adverse events. Healthcare providers should keep in mind that once a stable dosage of a long-acting opioid agent has been established for a patient, four to six weeks are usually required to assess pain and function.

The authors of the Archives article also recommend tramadol as a first-line pharmacological option for treating neuropathic pain. If clinicians are treating their patients with tramadol, however, they must be aware of its drug interactions, especially with selective serotonin reuptake inhibitors and monoamine oxidase inhibitors. Patients with a history of seizures or those receiving medications that can lower seizure threshold may be at an increased risk of seizures if they are taking tramadol.

The tricyclic antidepressant class has proved quite effective for neuropathic pain. But many TCAs are prone to a variety of drug-drug interactions and adverse events, and because TCAs possess sedative and anticholinergic properties, close monitoring is warranted in elderly patients.

"Neuropathic pain has long been poorly understood and consequently underdiagnosed. The treatment recommendations offer an evidence-based approach that allows for the use of traditional drugs with unconventional mechanisms of action in the treatment of neuropathic pain, said Tamira Mullarkey, M.S., R.Ph., clinical pharmacist at Irvington General Hospital, Irvington, N.J. Every patient has a unique response to therapy and vulnerability to adverse effects," she said.