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Opioids Effective Against Neuropathic Pain

Long-shunned drugs found to be a good treatment

WEDNESDAY, March 26, 2003 (HealthDayNews) -- Opioid medications, long stigmatized by patients and physicians alike, may now be poised for greater acceptance in the field of pain management.

A study appearing in the March 27 issue of The New England Journal of Medicine found that higher doses of the morphine-like medication levorphanol reduced neuropathic pain significantly more than lower doses of the same medicine.

A second study, this one appearing in the March 25 issue of Neurology, found that another opioid, OxyContin, decreased pain and improved sleep quality for people with diabetic neuropathy.

Neuropathic pain emanates from injury to the central or peripheral nerves and affects more than 2 million Americans. There are no clear guidelines on how to treat the condition, and many available drugs have had disappointing results, writes Dr. Kathleen M. Foley in an editorial accompanying The New England Journal of Medicine study.

Three broad categories of drugs are available to treat neuropathic pain, explains Dr. Russell K. Portenoy, lead author of the Neurology article and chairman of the department of pain medicine and palliative care at Beth Israel Medical Center in New York City. They are opioids, non-opioids and adjuvant analgesics, which are drugs that are for something else (for example, local anesthetics and antidepressants) but have been shown to work against pain.

Among those three groups, opioids have been the most controversial. "The positioning of opioid therapy for patients for chronic pain of all types, not just neuropathic, is evolving very quickly," Portenoy says. "Fifteen years ago, opioids were considered to be inappropriate for most patients with chronic pain. Now, in 2003, we have consensus statements from many medical societies that say opioids should be considered."

One reason for opioids' position on the margins of medicine is, of course, their association with addiction. They are classified as narcotics and are regulated by the Drug Enforcement Administration, which in itself is enough to make some doctors squeamish. There have also been issues regarding side effects and a perception that patients would develop a tolerance to the drugs, causing them to be ineffective, Portenoy says.

Another reason is that about a decade ago, some studies indicated that opioids were ineffective against nerve pain. "That controversy stood in contrast to a lot of clinical observation," Portenoy says.

Fast forward to 2003 and The New England Journal of Medicine article. In this study, 81 adults with neuropathic pain were randomly assigned to receive either high-strength (0.75 milligrams) or low-strength (0.15 milligrams) capsules of levorphanol for eight weeks.

The study authors picked the lesser known drug levorphanol over high-profile drugs such as methadone or morphine precisely because they wanted to bypass as much as possible any preconceived notions. Although the consent form clearly stated this was an opioid, the researchers felt levorphanol didn't have the same stigma.

Participants could regulate their own doses within certain limits so as to achieve the best balance between pain relief and side effects.

The high-strength capsules reduced pain by 36 percent, whereas the low-strength dosage reduced pain by 21 percent. These results are comparable to the effects of tricyclic antidepressants and the anticonvulsant gabapentin, both of which are commonly used to treat pain.

On average, patients in the high-strength group took 11.9 capsules per day while patients in the low-strength group took 18.3 a day, which was close to the 21-a-day upper limit allowed. Functioning and sleep were improved in both groups. And even though the trial lasted only eight weeks, participants did not seem more likely to escalate their dose by the end of the study, indicating that they were not developing a tolerance to the drug.

"Our study shows that [the drugs] clearly are effective," says study author Dr. Michael Rowbotham, a professor of clinical neurology and anesthesia at the University of California, San Francisco, and director of the school's Pain Clinical Research Center. "The higher-dose levels were more effective at relieving pain than the lower-dose levels, but it carried a price in terms of side effects."

Before the study ended, 59 patients (27 percent) withdrew, mostly because of various side effects, and more people dropped out in the high-dose group. The side effects of irritability and personality changes occurred only in the higher-strength arm of the study.

Certain types of pain disorders were also easier to treat than others. Only three out of 10 patients with brain injury-related pain (such as stroke) were able to complete the study. Individuals with pain from spinal cord injury or multiple sclerosis seemed to benefit greatly from the high-dose capsules.

Even though the drug didn't help everyone, it helped enough to earn it a place in the arsenal of pain medications, the authors state.

"The fundamental thing that was shown in these studies is that opioids can work for neuropathic pain. You can get adequate pain relief and you can do that without intolerable toxicities," Portenoy reports. "All of these controlled trials are creating a very strong evidence base that is refuting the perspective that neuropathic pain is unresponsive to opioids. It's very reasonable for doctors to now think about trying opioids."

More information

For more on the use of opioids in pain management, visit the American Pain Society or the American Academy of Pain Medicine.

SOURCES: Russell K. Portenoy, M.D., chairman, department of pain medicine and palliative care, Beth Israel Medical Center, New York City; Michael Rowbotham, M.D., professor, clinical neurology and anesthesia, University of California, San Francisco, and director, UCSF Pain Clinical Research Center; March 27, 2003, The New England Journal of Medicine
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