Key signaling protein associated with addiction controls the actions of oxycodone on pain

January 17, 2017, The Mount Sinai Hospital

RGS9-2, a key signaling protein in the brain known to play a critical role in the development of addiction-related behaviors, acts as a positive modulator of oxycodone reward in both pain-free and chronic pain states, according to a study conducted at the Icahn School of Medicine at Mount Sinai and published online January 17 in the journal Neuropsychopharmacology. The mechanisms of oxycodone action uncovered through this study will help scientists and physicians develop strategies and tools to dissociate the analgesic (pain relief) actions of opioids from the addiction-related effects.

Using mouse models of acute and chronic pain, Mount Sinai researchers found that RGS9-2, the intracellular protein that controls the function of opioid receptors in the brain reward center, promotes addiction to in pain-free, acute, and chronic pain states. Mice that lacked the gene responsible for encoding RGS9-2 (RGS9KO mice) showed less propensity to develop addiction-related behaviors. Furthermore, the loss of RGS9-2 function does not affect the acute analgesic effects of oxycodone. The research team also found that RSG9-2 plays a protective role towards the development of oxycodone tolerance, as RGS9KO mice became tolerant to the analgesic effects of the drug earlier than those that had the gene. Researchers found that the same mechanisms control sensitivity to oxycodone addiction in pain-free as well as states.

Oxycodone is a painkiller that is widely prescribed for acute and and is also among the most abused opioids. Oxycodone acts in the same brain receptors as morphine and heroin, the mu , which are present in many areas of the brain that mediate , but are also expressed in the network associated with addiction. While there has been extensive investigation into the mechanisms underlying the analgesia, dependence, and addiction potential of morphine, the mechanism by which oxycodone exerts its actions remained unknown.

"Although oxycodone produces similar analgesic and behavioral effects to those observed with morphine, our study demonstrates that the intracellular actions of morphine and oxycodone are distinct," says Venetia Zachariou, PhD, Associate Professor in the Fishberg Department of Neuroscience and The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai. "Our work reveals that intracellular factors that prevent the actions of morphine may actually promote the actions of oxycodone. This information is particularly important for pain management strategies, as a common course is to have patients oscillate between oxycodone and to achieve pain relief."

The Mount Sinai study provides new information on pathways involved in behavioral responses to oxycodone in pain-free and neuropathic pain states, which will help researchers and clinicians to determine the risks and benefits of oxycodone prescription for the treatment of pain. This knowledge may lead to the development of more efficacious and less addictive compounds for pain management.

Explore further: Oxycodone may be more dangerous than other addictive pain medication

Related Stories

Oxycodone may be more dangerous than other addictive pain medication

October 6, 2014
While all prescription opioids can be abused, oxycodone may be more potent in its ability to promote changes in the brain relevant to addiction.

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

February 24, 2014
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, ...

Limited dialyzability for oxycodone, noroxycodone

September 8, 2016
(HealthDay)—For patients with chronic pain with end-stage renal disease, oxycodone and noroxycodone have limited dialyzability, according to a study published online Sept. 2 in Pain Practice.

Antidepressants fine-tune brain reward pathway to lessen neuropathic pain

August 24, 2015
Commonly used antidepressant drugs change levels of a key signaling protein in the brain region that processes both pain and mood, according to a study conducted at the Icahn School of Medicine at Mount Sinai and published ...

Opioids produce analgesia via immune cells

January 17, 2017
Opioids are the most powerful painkillers. Researchers at the Charité - Universitätsmedizin Berlin have now found that the analgesic effects of opioids are not exclusively mediated by opioid receptors in the brain, but ...

Toward opioid vaccines that can help prevent overdose fatalities

December 7, 2016
In 2014, the number of deaths from opioid overdoses in the U.S. jumped to its highest level on record. The spike brought national attention to the epidemic and the awareness that new interventions are needed. Now researchers ...

Recommended for you

New wave of complex street drugs puzzles emergency doctors

August 21, 2018
At a time when drug overdoses are becoming more prevalent and lethal, a new report provides a snapshot of regional illicit drug use and, for the first time, highlights the complexity of detecting and treating patients at ...

Study finds racial disparities in prescribing opioids for chronic pain

August 20, 2018
Yale researchers have identified racial disparities in the treatment of patients who are prescribed opioids for chronic pain. Black patients who receive opioids long-term are more likely than whites to be tested for illicit ...

Proposal seeks to improve assessment of drug risks

August 20, 2018
A drug policy researcher is proposing a suite of changes to overhaul the Multi-Criteria Drug Harm Scale (MCDHS), which informs drug policies across Europe. The changes focus on addressing use and abuse separately, collecting ...

US approves first generic competitor to Mylan's EpiPen

August 16, 2018
US regulators Thursday approved the first generic alternative for the EpiPen, a life-saving emergency allergy medicine, two years after soaring prices for the original version owned by Mylan stoked controversy.

Study: What patients really think about opioid vs non-opioid medications for chronic pain

August 14, 2018
Prescriptions of opioids for chronic pain has increased dramatically since the 1990s in spite of their known harms. Despite a shortage of scientific studies on the long-term effectiveness of opioids such as morphine, oxycodone ...

Doctors nudged by overdose letter prescribe fewer opioids

August 9, 2018
In a novel experiment, doctors got a letter from the medical examiner's office telling them of their patient's fatal overdose. The response: They started prescribing fewer opioids.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.