Single genetic change may help cure morphine dependency

Washington, Jan 29 : Scientists have achieved a breakthrough in curing morphine dependency-one of the major side effects of its use as a painkiller-by genetically modifying a single trait on the surface of neurons.

This development by researchers at the University of California, San Francisco (UNSC) attains significance as it provides a drug target to prevent such a dependency.

Jennifer Whistler, an associate professor of neurology, points out that a majority of individuals are given the opiate drug morphine for extreme pain caused by cancer, surgery, nerve damage, and other conditions.

She says that, though it remains the painkiller of choice for many types of short-term pain, it is less useful for the treatment of chronic pain because its effectiveness decreases with continued use in a process called tolerance. Consequently, a larger dose is required to treat the pain, thereby increasing the chance of addiction.

The body's natural painkillers, such as endorphins, relieve pain by first binding to receptors on the surface of neurons.

Whistler says that the receptors cycle on and off "like a light switch", regulating the intake of endorphin. However, when the neurons encounter morphine, this crucial control is absent.

In the study, the research aimed to try to trick neurons into responding to morphine in the more regulated way. Whistler said that evidence has indicated that the natural on-off cycling occurs because the endorphin receptor withdraws from the cell surface, toward the cell's interior. The migration from the cell surface is called endocytosis.

Now, when the neuron receptors comes across morphine the light switch is broken, and the nervous system reacts by turning more tolerant of the drug, which makes the recipient more dependent on the drug.

In order to show their hunch that morphine's unwanted effects were caused by the inability of its receptor to withdraw from the cell surface, the researchers genetically engineered mice with a single difference from normal mice. Receptors that encounter morphine can undergo endocytosis in such mice, just like they normally do when endorphins are present.

It was shown that with this single change, morphine remained an excellent pain killer without inducing tolerance and dependence.

"As more pain medications are being removed from the market, new strategies to overcome chronic pain become crucial. If new opiate drugs can be developed with morphine's pain killing properties but also with the ability to promote endocytosis, they could be less likely to cause the serious side effects of tolerance and dependence," said Whistler.

She claimed that her study was the first to display that such a single cellular change could block the body's tendency to become tolerant of the drug.

Whistler is now testing a number of strategies to counter morphine addiction that include development of morphine derivatives like oxycontin, which are delivered in a time released manner or only once they have been processed in the digestive system.

Other approaches aim at developing morphine derivatives that target only certain opioid receptors but not others.

"The most promising aspect of these other approaches is that they have the potential to prevent or delay dependence and addiction to morphine, but few of them address the development of tolerance," said Whistler.

The research was published online "Current Biology" and appears in the journal's latest print edition.

ANI