The Brain Chemical That Hurts So Bad
Some people have bad backs and still walk through life. Others can't get out of bed. Some people with nerve pain gobble pills. Others grit it out. And often these different reactions come from people with equal injuries. Why?
Because they have different brains or, at least, different brain chemistry, says psychiatrist Jon-Kar Zubieta of the University of Michigan Medical School in Ann Arbor. In a new study, he and his coworkers have found that the same injury can trigger wildly different releases of a potent brain chemical in different people. Another new study points to a gene–acting on the same chemical–that appears to shield people from pain's onslaught.
The chemical is a neurotransmitter called dopamine. To check how it responds to pain, "we gave people an injection into the jaw for 20 minutes," says Zubieta, who published his findings in the latest Journal of Neuroscience. "It sounds nastier than it really is." The researchers asked for 25 healthy, pain-free volunteers and, through the needle, pushed harmless saline water into their jaws. The needle was small, and the amount of saline was tiny. But it was still uncomfortable. The volunteers rated their pain every 15 seconds.
The researchers also scanned the volunteers' brains to monitor chemical activity. Among those who rated their pain as the most severe, dopamine levels rose precipitously in one region of the brain associated with reactions to physical stimulation. And in another region, one associated with emotions, dopamine levels shot up among people who said they felt the most fear. "We know people feel chronic pain differently," says Zubieta. And more dopamine zinging around the brain, carrying messages of discomfort and fear, could explain the responses of those who feel it worst.
Dopamine has traditionally been linked to feelings of reward or impulses to move, but it may indeed be a pain culprit, too, says another researcher who has just identified a gene that seems to protect people against painful reactions. The gene is part of a cascade of reactions that get in dopamine's way, "so it's not impossible that there could be a connection between the two," says neuroscientist Clifford Woolf of Massachusetts General Hospital in Boston. He and his colleagues reported the results of their gene hunt Monday in Nature Medicine.
The researchers found a molecule called BH4, which shoots way up after nerve injury. This molecule affects the levels of a variety of neurotransmitters, including dopamine, and that chemical combo could add up to the agony felt by people with bad backs.
But there's a shield against this misery, and that's the gene Woolf found. For acronym-lovers, it's called GCH1. And Woolf has learned, after studying 168 back-surgery patients, that it comes in stronger and weaker versions. People with the stronger versions report less pain. "It has a protective effect," he says.
Only 25 percent of the population has that stronger version, however. Woolf is a partner in a pharmaceutical company now trying to synthesize that strength in drug form. "If we find a compound that blocks BH4, that does the same thing as the gene does, we could use it as medicine for people in chronic pain," he says. In the meantime, doctors might be able to screen patients before surgery for the weaker gene versions, and provide them more aggressive pain relief using existing drugs.
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