Pain drain

The brain mechanism behind chronic pain’s sapping of motivation

sorrow Fall 2014

Chronic pain, among the most abundant of all medical afflictions in the developed world, can trigger a psychic exhaustion best described by the question, “Why bother?”

A new study shows that a set of changes in key parts of the brain may explain chronic pain’s capacity to stifle motivation. The discovery could lead to entirely new classes of treatment for this damaging psychological consequence.

A series of experiments in mice led by Robert Malenka, MD, PhD, the Nancy Friend Pritzker Professor in Psychiatry and Behavioral Sciences, described in a study published in Science, showed that persistent pain causes changes in a deep-brain structure known to be important in the pursuit of goals likely to yield pleasurable results.

“We showed that those brain changes don’t go away when you transiently relieve the mice’s pain,” Malenka says. The experiments also indicated that the mice’s diminished motivation to work for rewards wasn’t the result of pain rendering them incapable of experiencing pleasure or from any accompanying physical impairment, he says.

Malenka and his associates looked at lab mice enduring chronic paw pain. The scientists trained the mice to poke their noses into a hole to get a food pellet. At first, a single nose poke earned a pellet. But over time, the number of nose pokes required for a reward was increased. In essence, the researchers were asking these mice, “How hard are you willing to work for food?”

A week later, tests showed that the mice had lost much of their work ethic, which wasn’t restored even when the pain was relieved. Malenka’s group further found that chronic pain permanently changed certain connections to a deep-brain structure called the nucleus accumbens, which is involved in pleasure seeking, and that a somewhat obscure brain chemical called galanin plays a critical role in this change.

The scientists identified receptors for galanin on certain nerve cells in the nucleus accumbens and demonstrated that disabling galanin’s signaling via this receptor prevented the long-term suppression of motivation seen in mice with chronic pain. This suggests that therapeutic compounds with similar effects could be developed, though they would have to be carefully targeted to avoid disrupting galanin signaling in other important brain circuits. 

Author headshot

Bruce Goldman

Bruce Goldman is a science writer in the Office of Communications. Email him at

Email the author