Forget the Pain, Literally

Using lessons from memory to treat chronic pain

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In medicine, pain management is a daily part of the job. Thankfully, there are a lot of good ways to treat “acute pain,” or pain at the moment of injury, like when a patient accidentally hammers a thumb instead of the nail. We mostly have acute pain figured out: aspirin for small bumps and bruises; opiates, such as vicodin, for the big stuff, like surgery.

However, for “chronic pain,” or pain that continues over weeks and months, we don’t really have good solutions. As a result, nearly 50 million Americans live with severe chronic pain almost every day for years. Cost-wise, chronic pain accounts for approximately $100 billion of the United States’ healthcare, according to the American Chronic Pain Association. Needless to say, pain is a problem.

Chronic pain is a lot like a puppy: it’s relentless in its excitability. Those with chronic pain say that the sites of their injuries will hurt a lot more than they should – even with a light touch.  And the more the pain occurs, the more likely it is to occur again, which is why failing to treat acute pain can lead to chronic pain later. Further, chronic pain seems to come and go many times throughout the day, often without a definable cause. The elusiveness and relentlessness of chronic pain gives it an air of mystery that can cause some doctors to doubt their patients. As treatments fail, some suspect that their patients aren’t being truthful, and are, instead, fueled by drug addiction or hypochondria.

For all of these reasons, there is no issue more in need of a creative solution than chronic pain. Luckily, a group of researchers in Quebec may have come up with just the thing. However, to understand how it works, you first need to understand the character of a memory.

Whether it’s the scent of perfume wisping across a crowded street, reminding you of your mother, or the crack of a baseball bat, reminding you of playing ball with your father, it’s amazing how a small trigger can bring back a flood of memories. But, our brains don’t discriminate: they dredge up the bad memories just as often as the good. Certain thoughts come whether you want them to or not, like when you’re at a loss for words on a date because all that comes to mind is the melody of “Sweet Caroline” (bum bum buuumm!).

Just as chronic pain comes and goes as it pleases, memories also seem to have a mind of their own – pun intended. You can’t force yourself to have a memory any more than you can make the sun set in the east. The only control we have over forming memories is when we repeat something over and over, hoping it eventually sticks. For anyone who’s ever had to study for a major exam, you know that, unfortunately, this is the only way.

And, you can’t willfully dispose of a memory either. Anyone who’s ever been heartbroken knows that his/her memory can’t be willed away. Not even when you close your eyes really hard and wish it to be. Like physical pain, a memory’s whim is not at the mercy of our desires.

Neuroscientists capture the capriciousness of memories by describing them as processes, not finite objects. What this means is that memories only exist at the moment when a network of brain cells fire in a certain way. You can’t point to a spot in the brain and go, “Aha! That’s where I remember where I put my keys,” because it’s the process of a bunch of nerves activating in a specific pattern at a specific time that make the memory. No one set of cells is dedicated to one memory, and many different memories may rely on the same cells.

The likelihood of a memory occurring has a lot to do with the strength of the connections between these cells, and, reciprocally, the strength of connection depends on the how many times the memory is recalled. For instance, when you look at a fact on the back of a notecard, the experience of observing that notecard will activate a certain set of brain cells. If you repetitively go over that fact, that set of brain cells will activate each time in a distinct pattern. When this happens, a process known as “plasticity” occurs, and soon those cells strengthen their connections with each other. Now when you try to recall that fact, you’re more likely to activate those specific cells in a specific way, and the memory comes back into existence.

As it turns out, pain also follows this pattern of plasticity. Like memory, pain occurs because a set of nerve cells in the spinal cord activate in a certain pattern, and the more those nerve cells fire together, the more connected they become. Therefore, chronic pain may be due to recurrent activity connecting a collection of nerves cells together when an acute pain is not stopped. Thus, if an acute pain occurs over and over, it is more likely to become permanent.

In addition, pain causes physical changes in the spinal cord, which sends pain signals to the brain, just as memory alters the brain. In the short term, memories and pain rely on shuffling around different proteins within the nerve cells to establish and strengthen connections. In the long-term, the cells must make completely new proteins to maintain those connections, and facilitate the activities of the cell.

Robert Bonin and Yves De Koninck, the researchers in Quebec, hypothesized that if, like memory, chronic pain needs to make new proteins to maintain those connections long-term, then maybe disrupting protein synthesis could block the pain. The results of the study were published in the journal Nature in February.

To test their hypothesis, the team injected ‘capsaicin’, the spicy chemical in peppers, into the paws of mice. This caused the mice to be more sensitive to pinches on their paws, and they would yank them away even when researchers pressed softly. They were able to measure this response by seeing how much pressure it took before the mouse would withdraw its paw from the pinch, giving a measure of how strong the pain connection was. They compared this result to how the mice reacted prior to injection.

Then the researchers injected the capsaicin mice with a blocker of protein synthesis while re-administering the capsaicin in the paw hours after the first injection. They found that it took the same amount of pressure to cause a response as it did before the mice had received any injections.

However, it wasn’t enough to give the protein synthesis blocker alone; the researchers also had to “recall the memory” of the initial pain, which is why the treatment only worked when giving another injection of the capsaicin simultaneously with the blocker. In a way, you can think of the re-injection of this capsaicin as a signal flare that tells the protein synthesis blocker where to act. More precisely, you can’t intervene in pain without it re-occurring because pain is a process, not a thing.

Finally, to complete their biological analogy, the researchers showed that many of the same proteins that are involved in maintaining memories were essential to forming the circuits for chronic pain in the spinal cord.

At the end of the day, Bonin and De Koninck took what they learned from memory formation and applied that knowledge to the spinal cord, creating a new treatment for chronic pain in mice. And while this approach is still a long way off from use in humans, the concept is truly promising.

We will probably never be able to stop accidents and injuries from happening. That’s just part of life. But, if the promise of this research is realized, perhaps we can someday learn to forget the pain – literally.

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