Researchers find new target to improve pain management

Sep 07, 2010

Researchers from Mount Sinai School of Medicine have discovered a major mechanism underlying the development of tolerance to chronic morphine treatment. The discovery may help researchers find new therapies to treat chronic pain, and reduce tolerance and side effects associated with morphine use. The findings are published in the July 20th issue of Science Signaling.

Overcoming tolerance to after chronic administration has been a persistent problem in treating patients with , including those with cancer and and recovering from major surgeries. After a week of morphine use, its effectiveness decreases as patients build tolerance, and patients also experience negative side effects like addiction and constipation. Researchers at Mount Sinai have identified changes in the brain and that occur during the development of morphine tolerance, providing a therapeutic target for preventing it and allowing for the identification of new therapies to treat pain with fewer side effects.

Led by Lakshmi Devi, PhD, Professor of Pharmacology and Systems Therapeutics at Mount Sinai School of Medicine, the research team studied changes in the abundance and signaling properties of a protein complex containing two different types of opioid receptors in the brains of mice. The protein complex, called a heterodimer, is made up of the mu receptor and one other called the delta receptor. After using a clever strategy to develop selective for the detection of the heterodimer in vivo, they found that this protein complex excessively accumulates in areas of the brain that process pain. Previous studies from Dr. Devi's lab have shown that signaling through this complex is associated with a reduced responsiveness to morphine over five days of treatment. Therefore, it is likely that the accumulation of this complex in pain-processing brain regions may be the cause of the development of morphine tolerance.

"We found that the brain selectively responds to chronic morphine by increasing heteromer abundance, blocking individual receptors from signaling the analgesic response to morphine," said Dr. Devi. "Now that we have identified a signaling complex associated with morphine tolerance, we can develop a drug that will block the delta receptor within this complex, allowing the mu receptor to signal for pain reduction." Dr. Devi's team will also work to find a drug that binds to the mu-delta receptor complex so that they can study how this receptor complex presents itself in other diseases as well.

"This finding may apply to more than just opiates," continued Dr. Devi. "We look forward to studying the behavior of similar receptor complexes in diseases like obesity, alcohol-induced liver fibrosis, and neuropathic pain itself."

Explore further: US scientists make embryonic stem cells from adult skin

Provided by The Mount Sinai Hospital

not rated yet
add to favorites email to friend print save as pdf

Related Stories

Morphine dependency blocked by single genetic change

Jan 28, 2008

Morphine’s serious side effect as a pain killer – its potential to create dependency – has been almost completely eliminated in research with mice by genetically modifying a single trait on the surface of neurons. The ...

Morphine blocks tumor growth

Jul 28, 2010

Current research suggests that taking morphine can block new blood vessel and tumor growth. The related report by Koodie et al, "Morphine suppresses tumor angiogenesis through a HIF1α/p38MAPK pathway," appears in the ...

Recommended for you

Leeches help save woman's ear after pit bull mauling

Apr 18, 2014

(HealthDay)—A pit bull attack in July 2013 left a 19-year-old woman with her left ear ripped from her head, leaving an open wound. After preserving the ear, the surgical team started with a reconnection ...

New pain relief targets discovered

Apr 17, 2014

Scientists have identified new pain relief targets that could be used to provide relief from chemotherapy-induced pain. BBSRC-funded researchers at King's College London made the discovery when researching ...

User comments : 0

More news stories

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

Study says we're over the hill at 24

(Medical Xpress)—It's a hard pill to swallow, but if you're over 24 years of age you've already reached your peak in terms of your cognitive motor performance, according to a new Simon Fraser University study.

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Ex-Apple chief plans mobile phone for India

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

Egypt archaeologists find ancient writer's tomb

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.