







Chronic pain is more than simply pain that lasts for a long time. Perhaps the easiest definition is pain that persists after the initial injury or illness that caused it - pain that has stayed longer than it should have or that serves no useful purpose.

Roughly 100 million Americans suffer some kind of chronic pain, according to the Institute of Medicine. The source of chronic pain varies widely - it could be back pain, migraines or arthritis. Cancer can cause chronic pain long after treatment is complete.

Some patients have conditions entirely defined by pain, such as fibromyalgia, which causes widespread muscle pain, or neuropathy, which can feel like a burning, tingling pain in the hands, feet or other part of the body.

"Chronic pain is not just prolonged acute pain. There are changes that define the chronic pain condition," said Allan Basbaum, a UCSF specialist in chronic pain research.

Both chronic and acute pain can affect a person's level of motivation, and the biological mechanism for that behavior change may be similar in both types of pain. But with acute pain, the reason for the motivation loss is beneficial. With chronic pain, it's not.

Fatigued, unmotivated

When people suffer acute pain - the kind that comes with serious injury or disease and fades away as the pain-inducing incident is dealt with - they also tend to become fatigued and unmotivated, pain experts say. And that makes biological sense.

In the case of serious disease or injury, often the best course for patients is to keep still and rest, and certainly to avoid any activity that causes more pain and, therefore, probably stalls healing.

Evidence from animal studies and human imaging has shown that, under conditions of acute pain, biochemical changes occur in the brain that may interfere with the mechanics of pleasure- and reward-seeking. The pain serves to prevent people from feeling the urge to get up and move around much - to seek out rewards.

Many pain experts believe that when pain turns chronic, the same biochemical changes happen, but they're no longer useful. Patients with arthritis, for example, may be physically able to pursue an active lifestyle, and even benefit from it, but changes in their brain may leave them completely lacking in motivation.

'Pain is useful'

"You always hear, 'pain hurts, but pain is useful.' With chronic pain, it's in no way useful," said Schwartz. "I really feel like we're looking at a failure of the system. It's a maladaptation."

In a paper published last month, Schwartz and other Stanford scientists identified a molecular pathway that, at least in mice, seems to link chronic pain and decreased motivation.

For the study, the scientists used two groups of mice - one group with a form of arthritis in a rear paw, and one with neuropathic pain. They compared both groups to mice with no pain.

The mice were put through tests to determine their level of motivation. The main test involved poking their nose into a small hole then scrambling across a cage to get a food pellet for a reward. After three weeks, the number of nose pokes the chronic pain animals were willing to provide dropped about 40 percent below the number the pain-free mice would do.

The mice in pain were just as physically able to provide nose pokes and cross their cages for a treat, the scientists showed. And the food pellets seemed to be just as tasty and rewarding to all of the mice, regardless of their pain. The mice with chronic pain just didn't want to work for their food.

When the pain was alleviated in mice they still lacked motivation, which suggests that any biochemical changes that occurred from the pain lingered for a long while, perhaps permanently.

"The animals undergoing chronic pain, they still would get some rewards, but they weren't willing to work as hard for the rewards. They gave up more easily," said Dr. Robert Malenka, senior author of the Stanford paper and a professor in psychiatry and behavioral sciences.

The scientists later looked at sections of the brains of the mice with chronic pain, focusing on an area called the nucleus accumbens, a major part of what's known as the "reward circuit" of the brain. In the nucleus accumbens, the scientists were able to identify molecular changes in one type of cell that can ignite or suppress reward signals.

They also found an increased uptake in the neurotransmitter galanin, which has been tied to everything from cravings for fatty foods to insulin control and muscle contractions in the gut. Galanin could play a key role in interfering with the reward circuit of the brain and, in turn, decreasing motivation, the Stanford scientists believe.

Link to motivation

In the mice, giving them a drug that blocked galanin seemed to help them recover their motivation. The same drug probably wouldn't be advisable for humans, because galanin has many functions throughout the body, most of which are useful. Plus, what's happening in the brains of mice may not match what's going on in the far more complicated human brain.

But identifying some of the molecular changes that may be involved in the ties between chronic pain and motivation at least offers hope that a drug therapy can be found, said Malenka.

"If this happens in a human in chronic pain - and that's a big 'if' - and if we can prevent it somehow, we may be able to treat a major morbidity associated with chronic pain that has largely been ignored," Malenka said.

Not a mental flaw

Short of a drug for specific emotional and mental problems caused by pain, hospitals and academic institutions around the country offer pain clinics for treating chronic conditions.

The treatments go far beyond providing pain killers. For many patients, dealing with the effects on their mood is more important to their quality of life than treating the pain itself.

The Stanford research and others like it may not offer new treatments or provide the full answer as to what's happening in the brain during pain. But some patients might find it reassuring to know that it's a biochemical change that's sapping their motivation, and not some mental or emotional shortcoming.

"These studies provide proof that something is really happening," said Dr. Darshan Patel, an anesthesiologist at Kaiser San Jose Medical Center who specializes in pain management. "Are we going to come up with a magic pill that we give to patients and their motivation returns? I don't think so. But it might help us convince more patients to get up and do something."
