Study: Chronic Pain Reprograms Hundreds to Thousands of Genes

Study: Chronic Pain Reprograms Hundreds to Thousands of Genes

Chronic pain changes everything from finances to relationships, and now new research from McGill University shows may reprogram the way genes work in the immune system.

“We found that chronic pain changes the way DNA is marked not only in the brain but also in T cells, a type of white blood cell essential for immunity,” said Moshe Szyf, a professor in the Faculty of Medicine at McGill in a press release. “Our findings highlight the devastating impact of chronic pain on other important parts of the body such as the immune system.”

Researchers analyzed DNA in the brain and white blood cells of rats, using a chemical known as a methyl group.

“Methyl marks are important for regulating how these genes function,” said study co-author Laura Stone, a researcher in the Alan Edwards Centre for Research on Pain.

They were surprised by the number of genes marked by chronic pain, saying that hundreds to thousands of different genes were changed.

“We can now consider the implications that chronic pain might have on other systems in the body that we don’t normally associate with pain,” Szyf added.

The following results were observed in the study:

  • There is a correlation between pain intensity and gene DNA methylation level in the prefrontal cortex.
  • Peripheral nerve injury is associated with DNA methylation changes in T cells.
  • Overlapping DNA methylation changes in prefrontal cortex and T cells.
  • DNA methylation states in T-cells are “predictors” of chronic pain.

The McGill researchers believe the new findings could advance the understanding of chronic pain, which could lead to new methods of diagnosing and treating chronic pain in humans. They also note that the findings could result in opening new directions in developing pain medicines that target the genes marked by chronic pain.

Their study, Overlapping signatures of chronic pain in the DNA methylation landscape of prefrontal cortex and peripheral T cells was published in the January issue of the journal Scientific Reports.

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Jean Price

Kerry…I’m curious how you finally got your diagnosis and started on the supplements you talked about. I found a doctor in Arizona who deals with Dercums and was wondering if you saw her. She is also and endocrinologist, but is extremely did icily to see since it appears she is the only one who is interested in lipoma type disorders. Not much money I. Them, I’d suppose!


Kerry- its a tragic comment on pain care to say a doctor wont respect the opinion of people in pain. I guess to them that is what being professional is all about.
Its good you have been able to find something’s that work for you. No doubt diet can make an important difference for people with pain and other illnesses. I have heard that raw beets- because they have a lot of nitrogen- to make nitric oxide can improve metabolic function. Beets also have betaine- and that helps methylation, as well. As many Americans are deficient in vitamin d, vitamin c, b vitamins, zinc, magnesium, salt -and medicine doesn’t test for those- the nutritional component of chronic pain is often neglected.Veganism has helped some as consuming animal flesh proteins stimulates insulin like growth factor- which stresses out metabolism. But as you know- nothing works for everyone. Some are hypomethylated- and some are overmethylated.
The researchers, the government, the health care industry- theyre about their own advantages and less about the public good. As you know- we all have to be our own best advocates - because our society is too selfish and egotistical to care much for individuals in pain.


Ok, two weeks ago I would have just past this article up and gone on with trying to link my 20 yr battle with severe pain that began after a stint with Cushings Disease from pituitary hyperplasia that I am just now finding that all along is related to Dercum’s Disease and I have the type II variety that caused thousands of tiny bb to marble tumors all over my body along with severe cognitive impairment. I mean I don’t even know how I’ve survived what I guess might be what many would be described also as severe fibromyalgia (something I knew and kept trying to get Drs to hear me when I said I have extremely painful lumps everywhere that wasn’t consistent with fibro but absolutely had the flu like and cognitive issues). Anyways two weeks ago I started taking L-methylfolate, and other supplements that influence methylation and NOTHING in 20 yrs has influenced my pain/sleep/cognitive function more! It’s much better! From what I understand is this has to do with the MTHFR Genetic mutation and CBS Deficiency. I’m still learning but I think this absolutely is related to my pain. I HAVE to take high dose opioids just to be able to live with this pain minute to minute and now I’ve cut them in half without any effort. I’ve never slept this good or thought more clearer. I hate that they report this study and other studies that amount to zero because nothing ever gets in the clinical setting so we are twisting in the wind for sure! And God help us if we go in to a Dr to say we think this or that is on to something that is causing or could help! Haha! They go bananas! It takes persistence and nightly trying to piece this together and then some luck added to 20yrs of never giving up. A near impossible task in this time that has me driving to one state for pain mgt from a true Pain Mgt Dr and then pass my state up going the other direction to fill the prescription! It’s just a travesty all the way around when you see the studies of studies going around and around for sure!

Augur Kythe

“be patient” my ass…

We are dying out here…

Dying in endless horrific pain and “doctors” do not care — they exploit my pain for their profit..


It is unfortunate that the research community has gotten too sloppy and careless- and that though the quantity of research has increased dramatically in the last 10 years- the quality has gone downhill. Despite recent efforts to improve transparency- a study done by JP Ioannidis et al looked at 442 research studies- only one study made raw data available to the public. So a lot of research is done the same way they make sausage- in a way you don’t want to watch.
But in addition to poor quality and lack of transparency, research is not effective. JP Ioannidis has pointed out that 85% of research is wasteful. In pain care- despite the fact that low back pain is the most frequent pain condition- most back pain is of unknown origin. Our researchers and research have failed terribly, in this regard. And they remain unregenerate.
This study about methylation- another example of poor research. For researchers are supposed to explain fully previous findings related to the variables tested. This study doesn’t, of course- for T cells aren’t the only variable related to pain. And so this study as to the growing incoherentism in pain research. That is why ” in a million studies, a light doesn’t have to shine through”. On the contrary, researchers are the blind men looking at the elephant-and they add to the blindness and confusion in pain care. A good example is migraine research- some will say Orexins are related to migraines- other CGRP, another vitamin a level, another mitochondrial insufficiency- this study might say t cell methylation. another cytokine levels, another will look at the connectome. Ball of confusion-that’s what the world of pain research is today. The public is left with confusing, conflicting, incoherent unreliable research-and most of it wont lead to any new or better treatments. So its clear there is a terrible lack of accountability in pain research and a terrible lack of focus on results for real pain sufferers. Research like this will continue to make empty promises- for the sake of obtaining more research monies, to boast falsely about the value of research. But frankly, is research lowering the prevalence of any chronic pain condition? Is research on pain helping to get peoples lives back or return them to work- or even lowering out of pocket expenses or the burden of treatment?


This isn’t specific to the study in the article, but I’ve a serious question. I have CRPS, type II (Complex Regional Pain Syndrome) and have noticed something that both troubles and frustrates me: All of the current and past studies regarding CRPS are for type I, never type II. No, I remember seeing 1 (just 1!) study for type II, but it was restricted to children under 16. Why nothing for adults with type II?? We suffer just as much as the children, perhaps more since we’ve likely had it much longer. Please pass this question on to your fellow researchers and scientists!!

Tim Mason

Dave you are spot on. I worked in pharma for 25 years. I was out there when the Barr and Parr fiasco came about. There was a legal battle over ibuprofen formulations we were working with and one company flat out lied about a stability study. In University research, it is all about getting grant money. In today’s research laboratory it is all about staying employed. If anyone is interested about what is going on concerning US research, please refer to This months copy of C&EN News - Dow/DuPont article.
As far as methylation taking place on proteins in pain suffers, (this could be an anomaly of the method used to determine methylation) I feel that is just about as significant as hydrolysis in the digestion food of pain patients.
NIH is a world within itself. Vast.
There is a great deal of “arm waving” when some of these researchers explain reactions that only exist in theory.
A good rule of thumb to use when looking at who is doing what research is “follow the dollars”


Dr. Goodwin- As Dr Virchow wrote- there are two causes of disease- pathological and political. I’m sure you know the politics of research better than yours truly. In 2014- a GAO report showed that there is little correlation between burden of disease and spending at NIH. Some interest groups- involved with cancer or elderly or specific disease like asthma or Lupus- seem to be able to get a disproportionate share of research funding at NIH. So clearly, that is evidence that NIH research is political.
As you know JP Ioannidis, Ben Goldacre, and some others have shown the many serious problems with reproducibility of research, of gaslighting in research, publication bias, methodological problems, and a low yield, etc. Yes this may be a problem with inadequate education- or that researchers don’t have folks like myself looking over the shoulder and asking questions. In addition, researchers, like providers- really don’t believe the public has a right to an opinion about what they do. The public is subject to “othering” and “discursive imperialism” by the health care industry” Perhaps that is why Congress started PCORI.
I also understand that much of research involves ” a calculus of probabilities and chances”. As Jacob Bernoulli indicated, statistics are used when you don’t understand nature. And whether it is migraines, low back pain, fibromyalgia- we can see the underdetermination of scientific theory and the decline effect in operation. So from where I stand- we lack the models in research and practice to meet the demands of people in pain.
We have institutional persistence forbidding evolution of better models and practices that may lead to better outcomes for people in pain. Although, adaptive research and interventions may hold promise- I don’t see much interest in that approach.
My being patient would only embolden our pain care system to do more of the same. And “insanity is doing the same thing over and over again and expecting different results”
It doesn’t take an Einstein to realize researchers and practitioners suffer from the same disease- that the dead weight of past generations weighs on them like a nightmare. As Freud put it you cant help those who are too attached to something and you cant help those who cannot form an attachment to something. Our researchers are too attached to methods that aren’t working and too proud to admit it. And the weight of the past and attachment to present methods weighs too much on people in pain who need our pain care system to lighten their load. It is time for those with identity foreclosure to overcome their excessive attachment to the ways of the past and chart a much different and better course for the sake of people in pain, for the sake of our Nation, and for the sake of humanity.

Jeremy Goodwin, MS, MD

@Dave, I understand your frustration but scientific research is unlike politics in that it is the pursuit of knowledge for its own sake and our understanding of the world within and around us. Only recently with the cut-backs in government funding and the sometimes intrusion of private enterprise into it has there become an increasing emphasis on potential or even the ‘promise’ of outcome and that is needed to convince those who fund projects of the value of the research, something often exaggerated out of necessity. Without such hopeful rational the finders cannot grasp the significance. And the significance is often unpredictable, many times far greater than anticipated. The potential gain stated is not necessarily a lie but something less predictable than it might otherwise seem on the surface and hence no time frame or accountability for it can be reasonably expected. Scientist create the dots of data that can float unconnectrd until another breakthrough or paradigm shift occurs to pull them together, either by teaching visionaries, researchers or R&D workers in industry. All must work together. And yes, much research is published in poorly monitored journals with inadequate statistical power and design to mean much, and This is due to poor education where the scientific method is taught. But do too does industry all over the planet operate in mediocrity with only a small minority able to carry the flag of change. We see this in politics too. It is the human way. So, Dave, try to be patient. We are making much progress along many fronts. This particular problem of pain medicine restriction and a relative witch hunt on practitioners and users of other controlled substances is, in my opinion , politically driven and poorly so with those who know better having to lay low to prevent loss of careers in the crossfire. That risk is real and I have experienced it. Another well phrased letter was published in the NEJM and reproduced here in this paper today. It states the obvious but the obvious needs to be stated. I am frustrated with the field. It makes me want to get out despite loving and caring much for my patients and being a first rate pain and headache specialist in neurology trained at Stanford and Harvard, and how I have served as both a chief of a university pain and headache service as well as having owned and run two private clinics and worked or trained in eight. It is frustrating for clinicians too. Please be patient. The tide must turn soon. There are many on the side of the patients but the authorities need to be reigned in and have to answer to somebody and drop the draconian isn rules and persecution that is causing much damage to the community of pain sufferers, and I am not convinced that it is doing much for those requiring addiction treatment since it is driving the old and new toward heroin at which point few are because then one becomes… Read more »

Doug Erickson

And leading Dr’s still tel you your pain level isn’t as important as your functionality, hopefully this will change, soon


Biomedical research has spent billions on pain research- with little to show for it. Genetic or “personalized” research is a gamble, at best. I understand Dr Collins at NIH and his associates are true believers in the value of genetic research. In 2000 he promised that by 2010 there would be all new types of treatments for disease based on genetic research. In 2010 he admitted he was wrong- and told Congress by 2020 there would be all types of new treatments for diseases based on genetics. Well its 2016 now- where are all those new genetic based treatments for migraine, arthritis, back pain?
We are duped by the designs of researchers- who are not accountable when their promises turn out to be empty. Worse then that a few years ago Dr Collins admitted that we had a reproducibility crises -and that NIH couldn’t fix it.
Reforms are needed in our researchers and their research. They are overconfident, sloppy and not focused on results. As JP Ioannidis, in more then one article has indicated, research in medicine has a very low yield- and there is a glacial pace of translation.
So I say to these researchers- I’ve heard it all before- but frankly research is about researchers boasting about how much they know- without regard to the benefits- or lack thereof to society.