Part of brain’s pleasure network curbed in mice with chronic pain

Relentless pain can sap a person’s will to exercise, work or socialize. The constant hurting may drain motivation by muffling nerve cells in a brain area involved with pleasure, a study in mice suggests. The results, published in the August 1 Science, may help explain why people who chronically ache could have trouble with treatments that require action, such as physical therapy.

“The natural response to the pain experience is to avoid and withdraw,” says psychologist Laura Simons of Boston Children’s Hospital. And nursing a wound can help acute injuries heal. But when pain turns chronic, that tendency to withdraw can persist beyond the point of being useful. By illuminating one way that long-term pain reduces motivation, the new study “legitimizes what chronic pain patients experience,” Simons says.

The results may ultimately lead to better drugs for disorders that involve reductions in motivation, such as depression, says study coauthor Robert Malenka of Stanford University School of Medicine.

Malenka and his colleagues tested motivation in mice by making them work for food. The animals had to poke their noses into a hole over and over again to get a food reward. After seven to 21 days of chronic paw pain, animals’ ambition waned and they earned less food, the researchers found. When food came for free, the mice in pain ate just as much as pain-free mice, suggesting that the trouble came only when extra effort was needed.

Temporary pain relievers didn’t eliminate the motivation drain triggered by two types of pain, nerve injury and inflammation. “It isn’t that the animal is experiencing pain and can’t physically do the nose poke,” Malenka says. Instead, the chronic pain made the mice unwilling to work for food.

Studies on the brains of these motivation-sapped mice revealed a difference in a particular group of nerve cells in the nucleus accumbens, an area involved in the pursuit of rewards. In response to chronic pain, these nerve cells showed signs of a weakened reaction to incoming signals. This lackluster response involved a protein snippet called galanin, a molecule thought to play a role in several brain processes including pain sensation.

Galanin and these nerve cells in the nucleus accumbens probably aren’t the only culprits behind the motivation drain, Malenka says. “I can virtually guarantee you that there are changes in other parts of the brain that are also important,” he says.