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Stanford Study Recruits Twins for Pharmacogenetic Study of Opiates

November 10, 2008

Opiates such as morphine and codeine are the primary prescription medication for pain relief, but just how well these drugs work varies significantly from patient to patient. And no one really knows why.

Certain patients may require 10 times the amount of opiates, also known as narcotics, to get the same level of pain relief as others. Side effects such as nausea or sedation can be debilitating to some, while nonexistent for others. Addiction potential also varies from patient to patient.

“We rely heavily on narcotics as the cornerstone medication for the relief of moderate to severe pain,” said Martin Angst, MD, associate professor of anesthesia at the Stanford University School of Medicine and one of two principal investigators in a new study exploring individual variations in reactions to opiate use. “Yet we don’t know a lot of things, like why some people ‘like’ narcotics more than others — that could be key in determining addiction potential.”

In an attempt to determine whether these variations are due primarily to environmental factors or inherited traits, investigators at Stanford are recruiting twins for a study titled “Opiate efficacy: a twin study.” The three-year study, funded by the National Institutes of Health, requires 125 pairs of twins to come in for one day of work in the pain research laboratory at Stanford.

“The core of the study is really to provide insight into what should be done to improve narcotic use in the future,” said Angst, the lab’s director. David Clark, MD, PhD, associate professor of anesthesia, is the other principal investigator on the study.

“If the causes of individual variations are primarily environmental, it would make sense to conduct epidemiological studies,” Angst said. “If the causes are primarily genetic, the next step would be to invest in studies of the genome that could uncover key genes regulating pain and analgesic pathways.” Such studies could uncover novel therapeutic targets and help guide the development of new pain medications. They could also lead to more rational pain therapies tailored to an individual’s genetic makeup thus reducing the risk of adverse events while optimizing pain control, Angst said.

Twins who volunteer for the study will have their pain sensitivity measured by using a mild heat probe and by immersing a hand in ice-cold water, both before and during an infusion of the opiate alfentanil. Researchers will also compare individual variations in levels of sedation, mental acuity, respiratory depression, nausea and drug-liking — a surrogate measure of addiction potential — between identical twins, non-identical twins and non-related subjects. This will provide an estimate of the extent to which variations in responses to opiates are inherited. For example, the finding that identical twins are more similar than non-identical twins would suggest inheritance plays a significant role in the effects of opiates.

The study was prompted by past genetic studies in animals that have shown a strong genetic component in the effects of opiates. Twins interested in volunteering for the study should contact Nick Phillips at nickphillips@stanford.edu or call (650) 721-6121.

Stanford University Medical Center integrates research, medical education and patient care at its three institutions — Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children’s Hospital at Stanford. For more information, please visit the Web site of the medical center’s Office of Communication & Public Affairs at http://mednews.stanford.edu.




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