Opioid abuse initiates specific protein interactions in neurons in brain's reward system

February 24, 2014

(New York) - Identifying the specific pathways that promote opioid addiction, pain relief, and tolerance are crucial for developing more effective and less dangerous analgesics, as well as developing new treatments for addiction. Now, new research from the Icahn School of Medicine at Mount Sinai reveals that opiate use alters the activity of a specific protein needed for the normal functioning of the brain's reward center. Investigators were able to block the protein, as well as increase its expression in the mouse nucleus accumbens, a key component of the brain's reward center. It altered the actions of opioids like morphine dramatically. The preclinical study, published online Feb. 24 in the journal Neuropsychopharmacology, is the first to show that opioid use changes activity of the protein RGS9-2 and alters both the threshold for pain relief and affects opioid tolerance.

"We were able to block addiction-related behaviors, but increasing the activity of the protein also lowered the pain relief response to morphine, and mice developed morphine tolerance much more quickly," said the study's senior researcher, Venetia Zachariou, PhD, Associate Professor, Fishberg Department of Neuroscience, Friedman Brain Institute, Department of Pharmacology and Systems Therapeutics, at the Icahn School of Medicine at Mount Sinai.

Dr. Zachariou explained that because the brain's reward center has such a strong impact on analgesic responses, non-opioid medications should be used for the treatment of severe chronic pain conditions. Pain specialists have several alternatives for the treatment of chronic pain. For patients that are already addicted to opioids, "an alternative pain medication could offer more analgesic relief without the adverse effects of opioids." Additionally, with this research in hand, the research team points out that targeting this molecule may eventually lead to a novel treatment for addiction."

In the study, investigators used a novel technique known as optogenetics, which allows the activation of specific neurons via blue light in real time, to determine the exact cell types of the brain reward center responsible for the reduced analgesic response.

"In our earlier work, by inactivating RGS9-2, we saw a tenfold increase in sensitivity to the rewarding actions of morphine, severe morphine dependence, a better analgesic response, and delayed development of tolerance," said the study's senior author. While opiate analgesics act in several brain regions to alleviate pain, their actions in the brain reward center may also affect analgesia. The nucleus accumbens may also affect the development of morphine tolerance, via mechanism that are distinct from those described in other regions of the brain.

Eric Nestler, MD, PhD, Nash Family Professor of Neuroscience, Icahn School of Medicine at Mount Sinai, praised the research. "These discoveries provide important new information about the role of the brain reward pathway in the analgesic responses to opiates".
-end-
The study was carried out in collaboration with Mary Kay Lobo, PhD, from the University of Maryland, researchers from the University of Crete, and Karl Deisseroth, MD, PhD, from Stanford University, and coauthors from the Icahn School of Medicine.

Opioid addiction is widespread and this research underscores the deleterious effects of its use. According to the National Institute of Drug Abuse, in 2010, 1.9 million Americans satisfied abuse or dependence criteria for prescription opioids.

About the Mount Sinai Health System

The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven member hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services--from community-based facilities to tertiary and quaternary care.

The System includes approximately 6,600 primary and specialty care physicians, 12-minority-owned free-standing ambulatory surgery centers, over 45 ambulatory practices throughout the five boroughs of New York City, Westchester, and Long Island, as well as 31 affiliated community health centers. Physicians are affiliated with the Icahn School of Medicine at Mount Sinai, which is ranked among the top 20 medical schools both in National Institutes of Health funding and by U.S. News & World Report.

For more information, visit http://www.mountsinai.org. Find Mount Sinai on: Facebook: http://www.facebook.com/mountsinainyc Twitter @mountsinainyc YouTube: http://www.youtube.com/mountsinainy

The Mount Sinai Hospital / Mount Sinai School of Medicine

Related Chronic Pain Articles from Brightsurf:

Researchers are developing potential treatment for chronic pain
Researchers from the University of Copenhagen have developed a new way to treat chronic pain which has been tested in mice.

Molecular link between chronic pain and depression revealed
Researchers at Hokkaido University have identified the brain mechanism linking chronic pain and depression in rats.

How chikungunya virus may cause chronic joint pain
A new method for permanently marking cells infected with chikungunya virus could reveal how the virus continues to cause joint pain for months to years after the initial infection, according to a study published Aug.

Gastroesophageal reflux associated with chronic pain in temporomandibular joint
Gastroesophageal reflux (GERD) is associated with chronic, painful temporomandibular disorder -- pain in the temporomandibular joint -- and anxiety and poor sleep contribute to this association, according to a study in CMAJ.

One step closer to chronic pain relief
While effective drugs against chronic pain are not just around the corner, researchers from Aarhus University, Denmark, have succeeded in identifying a protein as a future potential target for medicinal drugs.

Gut bacteria associated with chronic pain for first time
In a paper published today in the journal Pain, a Montreal-based research team has shown, for the first time, that there are alterations in the bacteria in the gastrointestinal tracts of people with fibromyalgia.

Nearly 5.4 million cancer survivors suffer chronic pain
A new report finds about one in three cancer survivors (34.6%) reported having chronic pain, representing nearly 5.4 million cancer survivors in the United States.

New opioid speeds up recovery without increasing pain sensitivity or risk of chronic pain
A new type of non-addictive opioid developed by researchers at Tulane University and the Southeast Louisiana Veterans Health Care System accelerates recovery time from pain compared to morphine without increasing pain sensitivity, according to a new study published in the Journal of Neuroinflammation.

New target for chronic pain relief confirmed by scientists
A research group at Hiroshima University observed a potential new target for chronic pain treatment.

Menopause symptoms nearly double the risk of chronic pain
In addition to the other health conditions affected by estrogen, it has also been shown to affect pain sensitivity.

Read More: Chronic Pain News and Chronic Pain Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.