The Footprints of Chronic Pain


A damaged nerve can give rise to pain that endures for months, years, or even a lifetime.

One line of thought says that if pain endures, then there must also be long-lasting changes, at the level of cells and molecules, to accompany it.

Now, using an established nerve injury model of chronic pain in mice, a new study suggests just that, by showing that enduring changes to the “epigenome”—the set of chemical modifications to DNA that determines which genes are turned on or off in an organism—may keep cells called microglia “primed” to contribute to future pain. 

Microglia are considered the immune cells of the central nervous system (spinal cord and brain), and are known to contribute to chronic pain

The new research was published May 24 in the journal Cell Reports.

Primed for pain?

A week after the surgery, the researchers saw that more than a dozen genes were turned on in microglia isolated from the spinal cord of injured mice, compared to their uninjured counterparts.

And, at the same time, these cells were left with molecular footprints or “marks”–36 in total–in the epigenome.

Specifically, the group identified a chemical modification made to histones, which are proteins around which DNA wraps, in the cells.

They also found that many of these molecular footprints were found near regulatory regions of DNA called “enhancers,” which are known to influence which genes are expressed over time scales as long as a cell’s lifetime.

Of most interest, when the investigators checked the microglia about a month after nerve injury, they saw that the changes in which genes were turned on in nerve-injured animals had vanished. Yet, out of eight histone marks the researchers had preselected to examine, a few were still there.

the marks could prime microglia for later pain, making them more likely to react in a harmful way during the pain signaling process.

Trying to definitively prove whether or not the molecular footprints identified in the current study contribute to chronic pain is technically difficult at the moment, as researchers lack a good experimental toolbox to do so

Regardless, Denk sees the current study as “a proof of principle—that you can have long-lasting epigenomic changes as a result of a chronic pain state.” – Matthew Soleiman  

Previous posts on the same topic, based on the same Kings College study:



One thought on “The Footprints of Chronic Pain

  1. painkills2

    For every level of pain you experience, your brain takes note and remembers. Which is why it’s so important to adequately treat acute pain before it becomes chronic or intractable. I don’t need to wait around for more research to tell me that.



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