Rare Gene Mutation Removes All Ability to Feel Pain
Sodium channel subunit could be a target for analgesics
WEDNESDAY, Dec. 13 (HealthDay News) -- Rare mutations in a gene encoding part of a sodium channel result in an inability to feel pain and could be a target for analgesics, according to a study reporting the discovery in six Pakistani patients. The finding is published in the Dec. 14 issue of Nature.
C. Geoffrey Woods, of the University of Cambridge in the United Kingdom, and colleagues studied individuals from three consanguineous families in northern Pakistan who were completely unable to sense pain due to a congenital defect. The index case was a 10-year-old boy who regularly performed "street theater," putting knives through his arms and walking on hot coals, who died on his fourteenth birthday after jumping off a house roof.
The researchers found that the defect was an autosomal-recessive trait that mapped to the SCN9A gene, which encodes a subunit of the voltage-gated sodium channel Nav1.7 that is highly expressed on pain-receptive neurons. The six affected individuals who were studied (not including the index case) had distinct homozygous non-sense mutations in this gene (S459X, I767X, W897X) and channels constructed with the mutant subunit were unable to pass current.
"Our data suggest that SCN9A is an essential and non-redundant requirement for nociception in humans," Woods and colleagues conclude. "These findings should stimulate the search for novel analgesics that selectively target this sodium channel subunit."
The study was partially funded by Pfizer.