Chic Trib

Science crosses pain threshold

Images of brain suggest mechanics of relief and why some suffer more

By Peter Gorner, Tribune science reporter

Published July 26, 2001

For the first time, neuroscientists have captured images of the brain coping with sustained pain, providing insights into the body's natural painkilling system and suggesting why some people are more sensitive to pain than others.

The power of endorphins to fight pain has been well known since the 1970s, when it was found that the brain produces chemicals far more potent than morphine, opium and heroin.

Now, University of Michigan scientists have published images that show the famous but elusive endorphins in action. And by recording people's perception of pain as the chemicals do their work, the researchers confirmed long-suspected links between brain chemistry and our senses and emotions.

People who claim to have a low tolerance for pain can find some ammunition here against skeptics. The study indicates it is possible their brains simply can't handle as much pain.

Coming as health advocates complain that severe pain often goes untreated, the study's findings may lead to more effective ways to relieve chronic and unnecessary pain and the psychological distress that accompanies it.

"It's very rare that we see a study that so ably puts together the psychological and physiological aspects of pain," said Dr. Kenneth Gruber, chief of the chronic diseases branch of the National Institute of Dental and Craniofacial Research, which funded the study.

Published this month in the journal Science, the study found that exposure to pain over 20 minutes caused a surge of endorphins in the brain. As the surge occurred, the subjects reported feeling less pain and fewer pain-related emotions.

Strikingly, the amount of perceived pain was not the same for everyone, though a computer ensured that all participants received a similar stimulus.

"We have shown that people vary both in the number of receptors that they have for these anti-pain brain chemicals and in their ability to release the chemicals themselves," said Dr. Jon-Kar Zubieta, who led a team of researchers from the University of Michigan Health System and School of Dentistry.

Those factors appear to determine how well people can cope with pain.

In the study, a high concentration of salt water was injected into subjects' jaw muscles, causing pain like temporomandibular joint disorder, or TMJ, an agonizing chronic condition that mainly afflicts women.

The technique was designed to bring about rapid and significant pain that also could be stopped quickly and completely. There are more nerves in the face than elsewhere in the body, making it more sensitive to pain. And the effects of the salt water, though painful, do not linger.

The volunteers--13 men and 7 women between the ages of 20 and 30--gave informed consent in writing and were aware that the experiment would hurt.

Pain is needed

Pain, essentially an indication that something is wrong, is critical to survival. The capacity to monitor the integrity of the body and to be made immediately aware of injury is vital, and individuals who are born without this capacity die young from injuries that they never felt.

When a person experiences pain, the body instantly responds to the sensation and the brain seeks to discover the cause. At the same time, stress causes the brain to produce natural opiates--endorphins and enkephalins--that lessen the perception of painful nerve signals, protecting us from fully feeling them.

Made in the pituitary gland, endorphins attach to receptors studding the outer surfaces of brain cells like chemical keys fitting into locks, numbing the pain message to the conscious part of the brain.

The potency of such chemicals is dramatically illustrated by the phenomenon known as runner's high.

"I'm a jogger and without endorphins kicking in, I couldn't run," Gruber said. "It just plain hurts too much. In fact, if you give runners drugs which block endorphins, we're stuck. Scientists think that many professional athletes are better than others not because they have more ability, but because they can withstand pain better."

Beyond general brain activity

Previous studies have pieced together the process by which the brain chemicals--called opioids--stop neurons from sending a pain message. Medical imaging also has revealed which areas of the brain respond most when a person is experiencing pain.

But the current study looked beyond general brain activity to focus on the chemical systems that suppress pain. The researchers also sought to accomplish something new: to relate the function of the chemicals to the volunteers' reports of what they felt.

Zubieta, who led the study, is a neurobiologist, psychiatrist and radiologist at the University of Michigan Medical School. In him, colleagues said, are blended the skills of an imaging specialist, an interest in psychiatric illness and the curiosity of a basic scientist.

Exposing the subjects to pain for 20 minutes, rather than limiting it to a few seconds as in previous studies, allowed Zubieta and the other researchers to achieve conditions much more closely related to chronic pain.

As the volunteers' brains were being scanned and the salt water was injected, they were asked to rate how much pain they were feeling every 15 seconds.

Afterward, the volunteers completed a questionnaire about how the experience made them feel. For comparison, each subject was also exposed to a placebo solution that does not cause pain.

Zubieta said the results showed not only that perceived pain decreased as the brain chemicals kicked in, but also that the chemical response was strongest in the regions where sensation and emotion are rooted.

"The higher the level of activation, the lower the scores the volunteers gave for pain-related sensations and emotions like feelings of the unpleasantness of pain," he said.

The intensity of the chemical response varied widely among volunteers. Those subjects who showed the strongest brain activity reported experiencing less pain--in other words, their endorphins protected them better.

"This may help explain why some people are more sensitive, or less sensitive, than others when it comes to painful sensations," Zubieta said. "Such variability in the pain-response system may help explain why some people react to pain and pain medications differently. It may also be quite relevant to why some people, but not others, develop chronic pain conditions."

Gruber agreed. "The study strongly suggests that there are people who have ineffective natural painkilling systems and gives us an impetus to create drugs which stimulate them directly, instead of using morphine and other painkillers that can cause problems," he said.

Insight on mental illness

The findings also may cast light on the connection between pain and mental illness.

"Many people who suffer from chronic pain have psychiatric symptoms," Gruber said. "And the question has always been: What came first?

"This study suggests that the pain causes the mental problems, not vice versa. If your coping system [the opioid system] is not reacting appropriately and is being overcome by the pain, the cause of your distress is physical, not psychological."

Copyright © 2001, Chicago Tribune

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