Researchers Identify a Brain Protein that Promotes Maintenance of Chronic Pain

Researchers Identify a Brain Protein that Promotes Maintenance of Chronic Pain

Researchers are hoping they’ve found a new target for the treatment of chronic pain, it’s a protein called RGS4

The discovery may help doctors stop acute pain from progressing into chronic pain. The research was conducted at the Icahn School of Medicine at Mount Sinai and published in print October 16, in The Journal of Neuroscience.

The transition from acute to chronic pain is accompanied by numerous adaptations in immune, glial, and neuronal cells, many of which are still not well understood. According to the press release, there is an imminent need for novel approaches towards the treatment of chronic pain and for the development of medications that disrupt pain states instead of simply alleviating symptoms.

“Our research reveals that RGS4 actions contribute to the transition from acute and sub-acute pain to pathological pain states and to the maintenance of pain,” says Venetia Zachariou, PhD, Professor in the Nash Family Department of Neuroscience, the Department of Pharmacological Sciences and The Friedman Brain Institute at the Icahn School of Medicine at Mount Sinai. “Because chronic pain states affect numerous neurochemical processes and single-target drugs are unlikely to work, it’s exciting to have discovered a multifunctional protein that can be targeted to disrupt the maintenance of pain.”

RGS4 is a multifunctional protein widely expressed in brain circuits that processes pathological pain, mood, and motivation. Through this study, Mount Sinai researchers observed that RGS4 plays an important role in maintaining pain states, regardless of whether the cause of pain was nerve injury or inflammation. Using genetic mouse models to ablate the gene expressing RGS4, the team demonstrated that prevention of RGS4 action disrupts the maintenance of chronic pain states in male and female mice.

Specifically, the research team used genetically modified mice to understand the role of RGS4 in the induction, intensity, and maintenance of chronic pain symptoms. They found that while genetic inactivation of RGS4 does not affect acute pain or the induction of chronic pain, it promotes recovery from sensory hypersensitivity symptoms in preclinical models of peripheral nerve injury, chemotherapy-induced neuropathy, and peripheral inflammation. Mice lacking RGS4 developed all expected symptoms of nerve injury, but they recovered within 3 weeks. Prevention of RGS4 action was also associated with an increase in motivation-related behaviors.

Dr. Zachariou’s laboratory team is continuing to conduct further investigation into the actions of RGS4 in the spinal cord and mood-regulating areas of the brain to better understand the mechanism by which this protein affects sensory and affective pain symptoms.

Authored by: Staff

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Research, research, research, research! [edit]! What about those suffering today? What about the billions that have been suffering for the past several years since this ignorance started? Where was the research then?
Oh that’s right, we had a little something called opioid medication that was a lifesaver to so many. Something small (that turned out to be big) something that didn’t cost much, something that helped give chronic pain victims somewhat of a normal life, something chronic pain patients had access to through there now terrified Physicians. Something that they took away over night, leaving us all alone to fight for our very lives. Four years of torture and horror stories with no help in sight and now they want to talk about research. Almost laughable…..

Thomas Kidd

People don’t be deceived by this evil [edit].

Thomas Kidd

I am not a mouse. More foolishness. What they won’t do to try to keep from using the only pain medication that actually works. I am so tired of the [edit]. Sorry I don’t feel very well.


Although this research is interesting, it almost surely won’t result in real-world help for any of us who are 60+. I hope it will help patients living with pain in the future.


Theres no need for “imminent” discoveries in pain management. That’s the talking point of overzealous, anti-opioid govt officials and drug companies looking to plague is with more antidepressants and gabapentanoids and the like. We already have meds that work plenty well for most ppl. They have few side effects and dont cost a small fortune for the average person. Opioids work. Stop making excuses for bad policy and scared drs. Start treating pain like it matters again!

That’s great. I hope that it doesn’t take 10 yrs to actually get offered to those people it can help. Meanwhile, those who suffer now can only try to endure the torture we are being put through.


I read an article on Google this morning @ why our pain medications no longer work. It said that there are more pharmaceutical lobbyist in Washington that there are law makers. Big Pharma is more interested in taking care of their shareholders. In my opinion this is why they have diluted the current pharmaceuticals. The big ones dont produce our pills, they are the middle man between the manufacturers, and the doctors. They sell our doctors a load of information and they in turn sell it to the patients. When the generics dont work, and 90% have more fillers than active ingredients. We try to go to the name brand, we can’t afford them so we have to take more generics. Big Pharma needs to check themselves. This is fraud. And it controls the FDA. According to another article I read there are only 30 FDA inspectors to inspect 30,000 manufacturing facilities. It also. Said that Chinese manufacturers are the dirtiest, and even when the inspectors call ahead to advise them they are coming to inspect, they do nothing. We buy 80% of our drugs from China.
When will the people we elected stop doing Big Pharma’s bidding, and do for the people who elected them. Are we complacent about what we put in our mouth? Not all the overdoses are opioid related. Check all your prescriptions, see who and where they were made and how many fillers they contain. Most contain lactose and silicone, starch, and many others. Care about yourself, and what you put in you body.


Now I have heard it all . We are dead!


They are going to cause more damage than they fix, IMO….

Debbie Nickels Heck, MD

That would be a lifesaving recovery for unknown numbers of people at this point. The tricks would be identifying which pts to screen, when to intervene, etc. It’s a good start.

Gail Honadle

Snake Oil. Injured parts of our body cause PAIN. Age causes PAIN. Use the research money to find a non addictive Pain Medication that doesn’t have Cancer causing agents in it or damages heart, kidney’s or liver.

Tasmanian poppy farmers are at the centre of the US opioid crisis, but they say they’re not to blame - ABC News

Needed next: a human probe for RGS4 studies.

The fact that this protein affects mood disorders, implies that it plays a role in psychiatric conditions ranging from substance abuse to schizophrenia.

It would be extremely wise to identify how this protein works in human mental illness.

To figure out why some rape victims or war survivors become intensely angry, fight their way to safety, then put the harm behind them, while other victims develop disabling post-traumatic stress disorders that harm them lifelong, might be profoundly helpful to folks who suffer PTSD.

What should not be done, is to create a race of human mutants who lack the RSG4 gene and pronounce them the future inhabitants of Earth.

Political interference in who is allowed to bear children has done vast harm and zero good during the 20th Century and must not be repeated in the 21st. Genetic diversity drives cultural evolution and society grows smarter from the variety of insights that a diverse population have. It’s disagreement that causes horse races, said novelist Mark Twain. Let’s NOT create some RSG4-knockout humans and pronounce them supermen.