In recent years, rigorous research has provided scientists with a detailed understanding of how pain signals travel from the skin and other organs to the brain. Different mutations in a single gene, however, demonstrate how much about pain remains mysterious: one worsens pain, while a second seems to prevent it.
The gene, known as SCN9A, produces a protein called Nav1.7, one of ten proteins that make up the sodium channels that dot the surface of axons and help propagate neural signals. Nav1.7 is found in specialized sensory fibers that respond to pain signals from throughout the body and transmit them to the spinal cord and brain.
Stephen G. Waxman, chairman of neurology at Yale, recently demonstrated that a mutation in SCN9A is responsible for hereditary erythromelalgia, a form of chronic and excruciating pain that causes the feet and other extremities to turn bright red when they become warm. Some people with this disorder cannot bear to wear shoes, for example, because the trapped heat brings on the pain. Some relieve the pain by soaking their feet in ice water.
Waxman and his team traced erythromelalgia to a mutation that affects Nav1.7 and causes sodium channels to open too easily, allowing an excessive influx of pain-causing sodium ions, and to close too sluggishly, allowing the pain impulse to linger.
However, a different mutation in SCN9A has scientists scratching their heads. This mutation has been shown to prevent people from experiencing any form of pain at all.
Pain-Free in Pakistan
Cambridge professor C. Geoffrey Woods and colleagues studied members of a family in northern Pakistan who apparently have never experienced pain and suffer an array of injuries as a result. The researchers were alerted to this disorder by stories of a boy who did street performances during which he would push the blade of a knife painlessly through his arm, or walk on burning coals.