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Amid Ongoing Controversy, Researchers Find Opiates Relieve Chronic Pain From Nervous System Damage


For release: Monday, May 12, 2003

A new study shows that opioid drugs taken orally could provide relief for some of the more than 2 million Americans suffering with chronic pain resulting from damage to the nervous system.

"The main point people should take away from this study is that opioids work for neuropathic pain, but they don't work for everyone," says lead author Michael C. Rowbotham, M.D., director of the Pain Clinical Research Center at the University of California-San Francisco (UCSF). "The benefits must be weighed against the drawbacks for each patient."

The study was funded by the National Institute of Neurological Disorders and Stroke and appeared in the March 27, 2003, issue of the New England Journal of Medicine .1

Whether to use opiates for chronic neuropathic pain has long been the subject of intense debate. Many physicians are reluctant to use these drugs because of the risks of addiction, tolerance, and side effects. Opiates, which derive from the poppy plant, include such powerful drugs as opium, heroin, morphine, and codeine.

Previous studies have shown opiates to be relatively ineffective for neuropathic pain in animals, and the animals typically develop tolerance over a short period of time, in that the drugs lose their ability to relieve pain. Furthermore, few controlled clinical trials exist to guide the use of opiates in humans with chronic neuropathic pain, even though they have been taken for centuries to relieve pain.

Complicating the issue, neuropathic pain is difficult to manage because of its variety of causes. Pain may arise from injuries of the central nervous system, such as in stroke, multiple sclerosis, or spinal cord trauma. It may also arise from focal injuries to the peripheral nervous system. The peripheral and central components of the pain pathways remain poorly understood.

To test the efficacy of the morphine-like opiate levorphanol, Dr. Rowbotham and his colleagues at UCSF randomly assigned adults with untreated chronic neuropathic pain to high- (0.75 mg capsules) and low-dose (0.15 mg capsules) groups under double-blind conditions. Patients in both groups self-administered tapered numbers of capsules up to a maximum of 21 per day. After an 8-week course of the drug, results showed that both high and low doses of the drug significantly reduced patients' pain.

The patients' pain relief was maintained with stable doses of the drug, and most patients chose not to take the maximum number of pills. These observations suggest that the patients did not develop tolerance and did not show signs of addiction, during the study.

Patients in both groups were asked to record the intensity of their pain, the degree of pain relief, and the number of capsules they took daily; the researchers also tested for psychological and cognitive function and blood levels of levorphanol. Patients taking the high-strength capsules averaged about 12 pills per day, whereas those on the low-strength capsules needed to take more, averaging 18 pills per day.

All patient groups reported pain relief from the treatment. The higher dose provided much greater pain relief than the lower dose - 36 percent reduction in pain compared to 21 percent, respectively. However, more people in the high-dose group dropped out of the study, complaining of a range of side effects, including restlessness, depression, and behavior changes. A small number of patients in the high-dose group reported symptoms of increased anger, irritability, confusion, or mood and personality changes.

This study is the first double-blind comparison of two dose levels of an opioid given to patients with the full range of neuropathic pain conditions, the researchers note. To prove definitively that levorphanol relieves chronic neuropathic pain, a comparison group of patients taking a placebo, or "sugar pills", would need to be part of the study. However, this approach is extremely difficult in pain studies, because patients in the placebo group would have to suffer pain throughout the trial.

Another reason the researchers opted not to use a placebo was that opiates have distinct side effects, making it virtually impossible to keep patients and clinicians from knowing who had taken which pills, Dr. Rowbotham said.

"Levorphanol in this study was effective for a broad spectrum of pain conditions," says Dr. Rowbotham. Because of the ongoing controversy about opioid drugs, he's cautious in discussing the implications of his findings. "Patients and physicians should consider opiates as one of the range of possible treatments for neuropathic pain, but opioid therapy is not for everyone," he said.

Researchers still know little about the long-term effects of levorphanol. More studies are needed to determine whether pain relief is sustained over a long period of time and whether tolerance or addiction become a problem over the long term.

The NINDS is a component of the National Institutes of Health in Bethesda, Maryland, part of the U.S. Department of Health and Human Services, and is the nation's primary supporter of biomedical research on the brain and nervous system.

- By Tania Zeigler


1 Rowbotham MC, Twilling L, Davies P, Taylor K, Mohr D, Reisner L. "Oral opioid therapy for chronic peripheral and central neuropathic pain." New England Journal of Medicine, March 27, 2003, 348:1223-32.



 

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Last Modified April 16, 2014