What a Pain!

UNC School of Medicine researchers have found a new treatment for chronic pain, which is pain that lasts for months and affects 116 million people. Scientists discovered an enzyme that blocks the reception of pain signals by sensors in the skin. It could lead to safer and more effective pain medications.

CHAPEL HILL — Under the Friday night lights on any high school football field, a sharp pain is pretty easy to identify. Football players from opposing teams run down the field, and, when their bodies collide, the players feel pain.

But in a lab in the Department of Cell Biology and Physiology at the University of North Carolina Chapel Hill School of Medicine, science is opening a window and a whole new way to look at pain.

“These colored dots are pain sensing neurons that have been colored with a chemical so we can watch what happens,” says Lipin Loo, a postdoctoral scholar in the Department of Cell Biology and Physiology at the University of North Carolina Chapel Hill School of Medicine. He’s showing a computer screen with dozens of multi-colored dots.

“Right now the neurons are feeling all right, but once I add a high dose of the chemical you can see the neurons are lighting up because they are firing and you are sensing pain,” says Loo.

The dots flash brightly for a split second. The flashes appear in groups, randomly, across the screen. If this is pain, how exactly does pain happen?

Basically, there are pain-sensing cells in your body called neurons. Those neurons have axons attached to them, which are little fibers that go out to your skin and your organs, serving as probes. Those axons are constantly sensing your body to see if anything is happening. If you cut yourself or break a leg, the probes are activated, sending an electrical signal along that axon, into your spinal cord and then up to your brain.

Once in the brain, the signals are passed to different areas that control emotion, thinking, and physical sensation.

"We call that acute pain, which is a type of pain that is important for survival,” says Dr. Mark Zylka, Associate Professor of Cell Biology and Physiology, at the University of North Carolina School of Medicine. “We obviously want to know when our hand or body part is injured so we can remove it from the thing that caused the pain.”

But pain becomes a problem when it is chronic rather than warning us about a danger.

While everyone from the players on the football field to office workers on the street experience acute pain now and then, more than 116 million Americans suffer from chronic pain. That’s about one quarter of the country. Chronic pain is defined as pain lasting 30 to 60 days or more. Chronic pain is usually generated by a more serious injury and the body handles chronic pain differently.

“If you injure yourself to where tissue is damaged, then pain becomes more of a chemical reaction because molecules are released from the skin,” explains Dr. Zylka. “We call this the inflammatory soup, which is made up of chemicals that act on the nerve fibers in the skin to make them super-sensitive.”

And that means those nerve endings are sensitive to even the slightest pain stimulus.

Here’s an easy way to understand the concept of chronic pain and it involves something we are all familiar with... Sunburn.

Because the skin tissue is damaged, the chemical soup is released, which makes the nerve endings in the skin super sensitive. That’s why even the slightest touch on the skin, even taking a shower, is so painful. The nerve endings have become hypersensitive.

You can see the difference when you look at chronic pain on the computer screen. With acute pain, the neurons still light up brightly on the initial jolt, but then as more jolts are sent to the neurons, the lights grow dimmer. Scientists say the receptors are becoming de-sensitized. It’s the phenomenon people call “getting used to it.”

But under conditions of chronic pain, the neurons never actually de-sensitize. The nerve endings continue firing, and, due to the sensitization created by the chronic soup, are constantly firing at the same level. That leads to chronic pain.

Back pain and arthritis are examples of chronic pain.

Besides being uncomfortable and, in extreme cases, debilitating, the problem with chronic pain is that current pain medications work well in the short term. But over time, those medicines can lose their effectiveness and there can be side effects such as liver damage. There’s also a serious danger of addiction.

And that’s what makes Dr. Zylka’s work so important. He’s found an enzyme that controls the chemical activity of the cellular receptors that signal pain. He also found that by reducing the level of the one enzyme, the numbers of molecules that trigger the cellular receptors are reduced. 

“We were studying what essentially is a complicated wiring diagram of how pain works and that led us to one molecule,” explains Dr. Zylka. “The eureka moment came as we were working with an animal model and discovered by hitting that one molecule we reduced the pain response.”

In other words, Dr. Zylka found an enzyme that blocks the signaling of pain at the first pain pathway. So, with the chemical receptors not working, the body doesn’t sense pain.

Researchers are working to identify other enzymes that could block even more pathways. They’re also consulting with other scientists about how best to incorporate the discovery into a medicine.

Dr. Zylka says his goal is to find as many pain-sensing neurons as possible and then, working with drug companies, try to get some of the targets moved into patients.

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