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Obscure brain chemical indicted in chronic-pain-induced "Why bother?" syndrome

Obscure brain chemical indicted in chronic-pain-induced "Why bother?" syndrome

why botherChronic pain, meaning pain that persists for months and months or even longer (sometimes continuing well past the time when the pain-causing injury has healed), is among the most abundant of all medical afflictions in the developed world. Estimates of the number of people with this condition in the United States alone range from 70 million to 116 million adults – in other words, as much as half the country’s adult population!

No picnic in and of itself, chronic pain piles insult on injury. It differs from a short-term episode of pain not only in its duration, but also in triggering in sufferers a kind of psychic exhaustion best described by the rhetorical question, “Why bother?”

In a new study in Science, a team led by Stanford neuroscientist Rob Malenka, MD, PhD, has identified a particular nerve-cell circuit in the brain that may explain this loss of motivation that chronic pain all too often induces. Using lab mice as test subjects, they showed that mice enduring unremitting pain lost their willingness to perform work in pursuit of normally desirable goals, just as people in chronic pain frequently do.

It wasn’t that these animals weren’t perfectly capable of carrying out the tasks they’d been trained to do, the researchers showed. Nor was it that they lost their taste for the food pellets which with they were rewarded for successful performance – if you just gave them the food, they ate every bit as much as normal mice did. But they just weren’t willing to work very hard to get it. Their murine morale was shot.

Chalk it up to the action of a mysterious substance used in the brain for god-knows-what. In our release describing the study, I explained:

Galanin is a short signaling-protein snippet secreted by certain cells in various places in the brain. While its presence in the brain has been known for a good 60 years or so, galanin’s role is not well-defined and probably differs widely in different brain structures. There have been hints, though, that galanin activity might play a role in pain. For example, it’s been previously shown in animal models that galanin levels in the brain increase with the persistence of pain.

In a surprising and promising development, the team also found that when they blocked galanin’s action in a particular brain circuit, the mice, while still in as much pain as before, were once again willing to work hard for their supper.

Surprising, because galanin is a mighty obscure brain chemical, and because its role in destroying motivation turns out to be so intimate and specific. Promising, because the discovery suggests that a drug that can inhibit galanin’s activity in just the implicated brain circuit, without messing up whatever this mystery molecule’s more upbeat functions in the brain might be, could someday succeed in bringing back that drive to accomplish things that people in chronic pain all too often lose.

Previously: “Love hormone” may mediate wider range of relationships than previously thought, Revealed: the brain’s molecular mechanism behind why we get the blues, Better than the real thing: How drugs hot-wire our brain’s reward circuitry and Stanford researchers address the complexity of chronic pain
Photo by Doug Waldron

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