When it comes to pain, people can be wimps, stoics or somewhere in between. Now scientists have found one reason -- a variation in a single gene that shows stoics really can tolerate more pain.
The discovery by University of Michigan neuroscientists emphasizes the need to customize pain treatment -- and might even allow doctors to try predicting which patients will respond to a certain kind of medication.
People's perceptions of pain are tremendously variable. A crushing blow to one person can be trivial to another. Likewise, pain medication that helps one patient may do nothing for the next.
The new research shows how much you suffer is due at least partly to a gene that helps regulate how many natural painkillers, called endorphins, that your body produces.
The gene produces an enzyme called COMT that metabolizes the brain chemical dopamine, which acts as a messenger between brain cells.
Everyone has two copies of this gene, one inherited from each parent -- but they can inherit forms that differ by one amino acid. The COMT gene that contains the amino acid methionine, or met, is less active than if it contained the amino acid valine, or val.
Dr. Jon-Kar Zubieta put 29 healthy young adults into brain-imaging PET scanners. He injected their jaw muscles with enough saltwater to make them really ache, simulating a painful condition called temporomandibular joint syndrome, or TMJ. Zubieta measured how their brain cells reacted while the volunteer victims rated, every 15 seconds, how much they hurt during the 20-minute pain cycle.
People who had two copies of the val-COMT gene were stoics. They withstood significantly greater saline doses than other volunteers while rating the resulting pain as less bothersome, Zubieta reports in the journal Science.
The PET scans verified that response: Painkilling endorphins were much more active in these people's brains.
In contrast, people with two copies of the met-COMT gene suffered the most pain from the smallest saline injections -- and had far less natural painkiller action.
People with both a met and val gene copy tolerated pain at levels between the two extremes.
A quarter of the U.S. population carries the "stoic" gene variation, while another quarter has the gene variant that makes them super-sensitive to pain, Zubieta estimates.
Why would a gene that regulates dopamine also affect painkilling endorphins?
Too much dopamine in the brain reduces endorphin content, Zubieta said. People with the double-val gene make a very potent COMT enzyme that clears out dopamine rapidly, triggering more endorphin production, while people with the double-met gene have the opposite reaction.
It's an important discovery, said neurobiologist Adron Harris of the University of Texas at Austin, who has long studied why men and women tolerate pain differently.
One reason: When standard pain medications fail, antidepressants that target dopamine sometimes relieve severe, chronic pain. But there has been no way to predict who might benefit. The new research suggests a simple gene test might solve that problem, Harris said.
"Certainly the need to individualize pain treatment ... is great, and is now done mostly by trial-and-error," he said. "This [research] is really getting to molecular medicine or genetic medicine, where you're using the genotype to predict which drug would be best for the person."
Pain response clearly depends on more than a single gene, Zubieta cautioned. For example, in another study, he found that women tolerate pain better during the time of the menstrual cycle when estrogen levels are highest.
And Zubieta's ultimate goal isn't just to predict pain tolerance, but to understand what combination of genetics and other factors make certain people more vulnerable to painful diseases, such as the joint-afflicting fibromyalgia that tends to strike women.