Mar 26 2009
The painkiller oxycodone is effective at treating the acute pain of shingles, an illness that often causes severe pain which can become long-lasting and sometimes even permanent.
The study, published in the April issue of the journal Pain, is one of the first to carefully evaluate different methods to relieve pain during a course of shingles, which many patients say causes the worst pain they have ever experienced. Effective pain treatment is crucial. Not only can the pain of shingles disrupt people's quality of life, but it is also possible that the less effectively the pain is treated, the more likely it will become a long-term problem that can change a person's life forever.
Shingles is caused by reactivation of the varicella zoster virus, the same bug that causes chicken pox, and only people who have had chicken pox are vulnerable to shingles. About 20 to 30 percent of people will get shingles at some point in their lives; the odds climb to 50 percent for people who live to the age of 85.
For most patients, the first symptom of the infection is pain, quickly followed by a rash where the pain first appeared. The rash appears most often on one side of the chest or face, oftentimes causing dozens of small pimple-sized lesions. Some patients also get flu-like symptoms like a headache and lethargy. The illness usually lasts about three or four weeks.
Pain is the hallmark and typically the most troubling symptom. Nearly all patients hurt to some degree, some severely. It's is a mix of pain that results from damage to nerves - known as neuropathic pain - as well as inflammatory pain in the skin and surrounding tissues.
"Oftentimes patients are told that the rash will heal in two or three weeks anyway, and the pain will go away, so they're not given something for the pain unless it's excruciating," said Robert Dworkin, Ph.D., the University of Rochester Medical Center pain expert who led the study. "But moderate pain can stop people from working, or enjoying their hobbies, and it can also make some people depressed or anxious. So there's good reason to treat all pain from the infection."
Doctors have a variety of choices to treat shingles pain. Medications like ibuprofen or acetaminophen are often used. More severe cases might call for use of Tylenol with codeine or oxycodone. But there haven't been placebo-controlled studies done to prove that any of these drugs actually work to treat shingles pain, said Dworkin, who is professor of Anesthesiology, Neurology, Oncology, and Psychiatry, and director of the Anesthesiology Clinical Research Center.
So Dworkin and colleagues studied 87 shingles patients in Rochester, N.Y., and Houston, Texas. The team studied the effectiveness of oxycodone and gabapentin, which both effectively treat pain associated with nerve damage.
The participants were divided into three groups and received oxycodone, gabapentin, or placebo. Patients, whose average age was 66, had moderate to severe pain. All patients also received an antiviral medication, which is standard treatment for patients with the infection.
The team found that oxycodone was quite effective. Patients taking the medication, which is sold as Oxycontin but is also available in other formulations, were more than twice as likely to experience a meaningful reduction in their pain - at least a 30-percent decrease - compared to their counterparts taking a placebo. Though the medication was effective, nearly one-third of the participants on oxycodone withdrew from the study, mainly because of problems with constipation.
The team was surprised that gabapentin did not appear useful to treat pain. Dworkin said it's possible that a higher dose would be necessary to adequately treat shingles pain. But the medication must be increased over the course of three weeks or more, which is often too long to have much of an effect on a fast-moving infection like shingles that can run its course in a few weeks.
The team chose to study oxycodone and gabapentin because they are often effective for treating patients in whom the severe pain of shingles persists for months or even years. In that condition, known as postherpetic neuralgia, the virus damages nerves during the shingles infection, and the pain then persists long after the shingles rash heals. The result can be terrible shooting pain, burning pain, the sensation of electric shocks in the body, or skin that is extremely sensitive to light touch.
"For some patients, even the light touch of a Q tip on their skin is excruciating," said Dworkin.
The shingles patients most likely to develop postherpetic neuralgia are those who are older, who have a more extensive rash, or who have severe pain during the initial illness. That's a big reason why initial pain treatment may be so crucial, Dworkin said.
Doctors estimate that overall, about 1 out of 4 or 5 patients with shingles who are treated quickly with antiviral medications will develop postherpetic neuralgia. For older patients not treated with antivirals, the odds of getting postherpetic neuralgia jump to 40 to 50 percent.
It was Dworkin who, in 2007, headed a group that published the first international consensus guidelines for treating shingles. The guidelines call for definite use of antiviral medications in all patients older than 50 years of age, and in younger patients under certain conditions, as well as consideration of a broad group of medications ranging from over-the-counter drugs like ibuprofen to Tylenol with codeine or oxycodone.
In 2007 he also led an international group of scientists who came out with the first international treatment guidelines for neuropathic pain. He is the founder of the International Conference on the Mechanisms and Treatment of Neuropathic Pain, which meets annually.
Funding from the National Institute of Neurological Disorders and Stroke provided the impetus for the study, which was funded directly by Novartis and Pfizer. Endo, Novartis, Pfizer, and Purdue Pharma provided medications and placebo for the study. In the past year, Dworkin has consulted with or spoken on behalf of Endo and Pfizer as well as several other companies and organizations that fund pain research or produce medications designed to alleviate pain.
In addition to Dworkin, other authors include, from Rochester, Richard Barbano, Karl Kieburtz and Cornelia Kamp of Neurology; Robert Betts of Medicine; Janet Pennella-Vaughan of Anesthesiology; and Michael McDermott and Carrie Irvine of the Department of Biostatistics and Computational Biology.
Other authors include Stephen Tyring of University of Texas Health Science Center; Gary Bennett of McGill University; Erhan Berber of Novartis Pharmaceuticals; John Gnann of the University of Alabama at Birmingham; Mitchell Max of the University of Pittsburgh; and Kenneth Schmader of Duke University.