14 March 2010

Mutations in the SCN9A gene and pain sensitivity

The article emphasizes the genetics, but I'm more interested in the implication that the heightened sensitivity relates to the speed at which sodium channels close in nociceptive neurons.

Gene Linked To Pain Perception - Science News: "Gene linked to pain perception
Common genetic variant makes some people more sensitive
By Laura Sanders
Web edition : Monday, March 8th, 2010

The team found that people who reported higher levels of pain were more likely to carry a particular DNA base, an A instead of a G, at a certain location in the gene SCN9A. The A version is found in an estimated 10 to 30 percent of people, Woods says, though its presence varies in populations of different ancestries.

The same trend — higher pain levels reported by people who carried the A — held true in cohorts of people with other painful conditions including sciatica, phantom limb syndrome and lumbar discectomy.

The genetic variation affects the structure of a protein that sits on the outside of nerve cells and allows sodium to enter upon painful stimuli. The sodium influx then spurs the nerve cell to send a pain message to the brain.

This channel protein is a promising target for extremely specific and effective pain drugs, Waxman says: ‘Given that this channel has been indicted, it would be nice if we could develop therapeutic handles that turn it off or down.’

Researchers already knew that people with mutations in SCN9A can have extreme pain syndromes. Genetic changes that render the protein completely inactive can leave a person impervious to pain, although otherwise healthy. Other mutations can lead to conditions such as ‘man on fire’ syndrome, in which people experience relentless, searing pain.
In additional laboratory studies, the researchers found that nerve cells carrying the A variant of the gene took longer to close their sodium gates, allowing a stronger pain signal to be sent to the brain. Nerve cells carrying the more common G version of the gene snapped shut faster, stopping the pain signal sooner. "