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Key Concepts

• Human beings at large differ in how sensitive they are to pain. Much of the variation is apparently random. But gender matters. Women tend to hurt more than men do. Ethnicity can also interface with ache; some ethnic groups are more tolerant of discomfort than others are.
• In the past few years researchers have begun unraveling the genetic roots of these differences. They are also pinpointing social, cultural and psychological components that play parts in pain sensitivity.
• Assessing patients’ vulnerability to anguish may be essential to accurately judging the severity of their condition. It is also critical to deciding how to treat individuals’ pain. Revealing the molecular causes of individual variation in pain perception is already providing potential targets for novel pain medications.

One day as a child Billy Smith (not his real name), a resident of Newfoundland, could not take off his shoe. No amount of twisting or tugging would loosen its grip on his foot. The reason for his struggle eventually surfaced: a nail had pierced the sole and entered Smith’s flesh, tightly binding the two. Removing the nail freed the foot, but solving that problem only underscored a bigger one: Smith had not noticed.

Smith is among a tiny cluster of people, fewer than 30 in the world, who harbor a genetic quirk that renders them incapable of perceiving pain. “These humans are completely healthy, of normal intelligence, but don’t know what pain is,” says clinical geneticist C. Geoffrey Woods, who studied a group of such patients from northern Pakistan. They can sense touch, heat, vibration and their body’s position in space. Yet for them, root canals are painless, as are falls, fires and whacks on the head with a baseball bat. One woman with so-called congenital indifference to pain (CIP) delivered a baby without discomfort.

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