Gene determines susceptibility to pain
Some people can bear physical pain that stops others in their tracks, a feat often attributed to mental toughness. But resistance to pain can also be genetic, according to a report published online this week in Nature Medicine from researchers at Massachusetts General Hospital.
The scientists identified a common genetic variation in humans that affects pain sensitivity. People who inherit a protective form of the gene feel acute pain less, and are resistant to developing chronic pain after an injury or surgery.
Researchers found that activity of an enzyme called GCH1 increased after nerve injury in rats, resulting in higher levels of a metabolite called BH4. BH4 is required to make a number of pain-producing neurotransmitters in rats and humans. Giving the rats a GCH1 inhibitor resulted in the animals showing fewer signs of pain, while injecting them with BH4 made them display more signs of pain.
These results led the researchers to look for genetic differences in GCH1 activity in people reporting varying levels of chronic pain. They studied 168 patients who had undergone back surgery and found that one variant of the GCH1 gene was significantly more common in those who did not report persistent postsurgery pain. It was less frequent in those who developed chronic discomfort.
The variant also affected the experience of acute pain. Healthy volunteers who carried the protective sequence showed reduced production of BH4. They could also withstand being poked, exposed to heat, or subjected to a tourniquet on their arm longer before asking the researchers to stop.
The work uncovers a previously unknown pain pathway, say the researchers, led by Clifford Woolf of MGH. Chronic persistent pain following surgery, injury, or stemming from arthritis affects as many as 50 million people in the United States. The study opens up the possibility of genetic screening for susceptible individuals and the development of new pain medication targeting GCH1 activity.
Bottoms up for heart health
Men sticking to a heart-healthy lifestyle by exercising, eating right, and not smoking can still benefit from adding a daily drink or two to their routine, according to a new study from researchers at Beth Israel Deaconess Medical Center and the Harvard School of Public Health.
Studies have previously shown that men who drink moderately have a lower risk of heart attacks, but it has not been clear if the reason was the drinking or other aspects of their lifestyle. Men who drink moderately may also exercise and eat in moderation, confounding attempts to detect only the effects of alcohol.
To get around that issue, Kenneth Mukamal and colleagues studied a group of 8,867 male health workers chosen for their admirable lifestyles. The men were not overweight; they exercised daily, didn’t smoke, ate a healthy diet, and took multivitamins. The researchers tracked the subjects’ alcohol consumption for 16 years and compared the incidence of heart attack among men with different levels of alcohol intake.
They found that men who consumed between one-half and two drinks daily had a 40 to 60 percent reduction in risk of heart attack compared to those who had fewer drinks or didn’t drink at all. There was a limit, though. More than two drinks per day all but erased the benefits.
The benefits attributed to drinking in this healthy group were as large as those measured in other studies for the general population and were as large as the positive effects of diet, exercise, or maintaining a healthy weight.
“Our results suggest that moderate drinking could be viewed as a complement, rather than an alternative, to these other lifestyle interventions,” the authors write in the Archives of Internal Medicine.
