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To tame chronic pain, erase brain’s memory

MCGILL (CAN) — Researchers have discovered that it may be possible to ease chronic pain by erasing memories stored in the brain.

It has long been known that the central nervous system “remembers” painful experiences, that they leave a memory trace of pain. And when there is new sensory input, the pain memory trace in the brain magnifies the feeling so that even a gentle touch can be excruciating.

“Perhaps the best example of a pain memory trace is found with phantom limb pain,” suggests neuroscientist Terence Coderre of McGill University. “Patients may have a limb amputated because of gangrene, and because the limb was painful before it was amputated, even though the limb is gone, the patients continue to feel they are suffering from pain in the absent limb.

“That’s because the brain remembers the pain. In fact, there’s evidence that any pain that lasts more than a few minutes will leave a trace in the nervous system.”

It’s this memory of pain, which exists at the neuronal level, that is critical to the development of chronic pain. But until now, it was not known how these pain memories were stored at the level of the neurons.

Recent work has shown that the protein kinase PKMzeta plays a crucial role in building and maintaining memory by strengthening the connections between neurons.

In the new research, published in the journal Molecular Pain, Coderre and colleagues have discovered that PKMzeta is also the key to understanding how the memory of pain is stored in the neurons. They were able to show that after painful stimulation, the level of PKMzeta increases persistently in the central nervous system (CNS).

Even more importantly, the researchers found that by blocking the activity of PKMzeta at the neuronal level, they could reverse the hypersensitivity to pain that neurons developed after irritating the skin by applying capsaicin—the active ingredient in hot peppers. Moreover, erasing this pain memory trace was found to reduce both persistent pain and heightened sensitivity to touch.

Coderre and his colleagues believe that building on this study to devise ways to target PKMzeta in pain pathways could have a significant effect for patients with chronic pain.

“Many pain medications target pain at the peripheral level, by reducing inflammation, or by activating analgesia systems in the brain to reduce the feeling of pain,” says Coderre.

“This is the first time that we can foresee medications that will target an established pain memory trace as a way of reducing pain hypersensitivity. We believe it’s an avenue that may offer new hope to those suffering from chronic pain.”

The research was supported by grants from Canadian Institutes of Health Research, the Louise and Alan Edwards Foundation, the National Institutes of Health, and an Astra-Zeneca/AECRP fellowship.

More news from McGill University: www.mcgill.ca/newsroom/

chat11 Comments

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11 Comments

  1. Tan

    Terence,

    Would your research also apply to excruciating relationships? There seems to be a synergy here! :)

  2. Jesper Seest Mogensen

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  5. Diane H

    Having suffered from chronic nerve pain for many years, I hope this research continues at a rapid pace. Nerve pain is the worst; nothing helps, nothing at all.

  6. Jeff K.

    Fibromyalgia, likely trigered by hip replacement surgery, forced me to leave work at age 53. Several close relatives also suffer from this painful, chronic auto-immune condition. Lyrica and the new drug Seleca have helped, but I still rely on prescription analgesics which are effective but come with their own baggage. I will be following research in this area with great interest.

  7. Julie

    I think we need to tread carefully. How does PKMzeta affect other memory formation? It seems like a lot more research needs to be done here.. we need to see if PKMzeta affects other processes in the brain. Either way, this is definitely a ray of hope for the enormous number of chronic pain patients out there. Science is taking us to new and amazing levels, striving to explain what we one day never thought possible.

  8. metta hansen

    I hope you are well-advanced in your research. Between degenerative disk disease, fibromyalgia, and the more localized pain in my neck and lower back, I don’t know how much more i can stand. As for memories being stored in the brain, I have seen that in my life many times. I think you’re onto something. Thank goodness for people like you.

  9. metta hansen

    I made no duplicate comment. This is my first visit to this pagel I think “Post” was unresponsive the first time I clicked it (this happens to me so often that I click again). So that is probably how a duplicate was created.

  10. Terence Coderre

    Since many brain areas use PKMzeta to store memories, the PKMzeta inhibitor we used (ZIP) would likely affect other memories. For this reason, additional research is needed to determine how to target PKMzeta inhibitors specifically to neurons in the pain pathways. As we administered ZIP within the spinal cord in laboratory animals, it did not affect conscious memories. However, even after required safety trials, it is not practical to administer such drugs to the spinal cord in patients. As for using it for mental anguish, this would be even more difficult, as erasing specific negative conscious memories and leaving others, seems unlikely even in the distant future.

  11. Wendy Ritchey

    I’m wondering if anyone at Stanford or anywhere else in the Bay Area is doing any studies using PKMzeta to alleviate PTSD symptoms. I have a patient who’d like to participate in such a study.

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