Scientifically Speaking | The boy who felt no pain
Geoff Woods, a geneticist at the University of Cambridge, had heard reports of a ten-year-old boy in northern Pakistan who was performing dangerous stunts in street performances. The boy walked over burning coal and lacerated his arms with knives, but surprisingly never actually feeling any pain. Tragically, the boy died before Woods could even meet him. Impervious to pain, but not to injury, he jumped off a roof before his 14th birthday.
In Pakistan, Woods’ research team found others from the Qureshi biradari with the same rare condition. All of the family members who felt no pain had suffered injuries to their lips and tongue due to self-harm in the absence of a deterrent. All of them had also suffered bruises and cuts. Most of them had broken bones many times; some were unable to use their limbs. There was a reasonably high frequency of this condition in the clan due to intermarriage.
In 2006, Woods’ team painstakingly identified the genetic change that was the cause of this condition. He found that though the sense of pain was gone, those who suffered from the genetic variation, could sense pressure and touch. They were of normal intelligence. However, oddly enough, the sense of smell was also missing along with pain.
Since that time, only a few other people with this genetic change have been reported in medical literature. In all cases, those who feel no pain have had to adjust to a world containing sharp edges, hard objects, and hot liquids. They’ve endured fractures, chewed off lips and tongues, bruises, cuts, and burns. Not feeling pain is extremely dangerous, since pain has a protective purpose. Pain warns us of danger.
In contrast to the inability to feel pain, another genetic condition has also been observed in some other people. There is an excruciating state of feeling too much pain, which is known as “man-on-fire” syndrome. Simple tasks like putting on clothes, walking, or even entering a warm room can feel like burning to those afflicted with it.
Stephen Waxman, a researcher at Yale University, has spent over a decade investigating this condition. In 2007, Waxman reported the discovery of a boy who had episodes “like hot lava” lasting from minutes to hours. These painful episodes were sparked by exercise, consuming caffeine, ingesting large amounts of sugar, or even occasionally eating melon. The boy wore open-toed sandals or went barefoot. He submerged his hands and feet in ice water for relief. Waxman found that the boy’s relatives over six generations had also suffered from similar symptoms.
Both of these conditions are caused by mutations to a gene known as SCN9A, which contains instructions on how to make a protein called a voltage-gated sodium channel. The gene works in neurons that are located outside the brain and spinal cord. Voltage-gated sodium channels react to changes in electrical signals. They open and let sodium ions enter and change electric charges flowing through neurons. The SCN9A gene gives rise to a particular channel called Nav1.7 involved in pain perception.
In Pakistan, Woods had found people who had a “loss of function” mutation where Nav1.7 didn’t work properly. Consequently, they felt no pain. On the other hand, Waxman had identified a “gain of function” mutation that caused people with a variant Nav1.7 to become hypersensitive to pain.
Scientists don’t know precisely how Nav1.7 works in pain perception, but pharmaceutical companies are in a race to develop painkillers to dampen its effects. A few of them have progressed as far as clinical trials.
Earlier this year, scientists published a report of a gene-therapy system used to target the SCN9A gene. They created a system that temporarily lowers the activity of Nav1.7, to reduce sensitivity to pain. The work was done in mice, so there is still a steep hill to climb before it is determined to be safe and effective in people. And even if it effective, if side effects include temporary loss of smell, then it might not be the right approach.
It is clear, however, that we desperately need a new generation of painkillers. One out of five adults is estimated to suffer from some form of chronic pain. Current pain drugs like opioids are not specific: they interfere with many senses, and are addictive. Over time, patients can require higher doses for the same effect as they build up tolerance. Opioids can also have serious side effects.
Other drugs available over the counter are not effective enough for chronic or severe pain. Clearly, it would be great to have drugs that could block pain when needed without causing addiction or harming the body.
After all, pain is not abstract. When I am asked to visualise excruciating pain, I remember my grandmother as she succumbed to cancer, eventually suffocating from an accumulation of fluid and cells in her disintegrating lungs. Being able to lower the dial on pain would help many people going through tremendous suffering like my grandmother. It would make surgery and chemotherapy more tolerable.
Treatment of pain should not remove the ability to feel it, but should make it manageable. As the boy in Pakistan and the boy who felt his body was burning like lava found out, both the absence of pain and too much of it can make life unendurable.
Anirban Mahapatra, a microbiologist by training, is the author of COVID-19: Separating Fact From Fiction
The views expressed are personal