A study of people with a congenital inability to experience pain identifies a key player in the molecular basis of pain perception.

Members of three related families in northern Pakistan have inherited a very rare condition: the complete inability to sense pain. The first family member studied was a ten-year-old street performer whose inability to feel pain enabled him to place knives through his arms and walk on burning coals. (Sadly, the boy died before his 14th birthday from injuries sustained after jumping off a roof.) The cause of the condition has now been tracked down to a defective voltage-gated sodium channel, Nav1.7.

Three lines of evidence led to Nav1.7 being a prime suspect in pain perception. The channel is present at high levels in neurons that detect painful stimuli. It is excessively active in people with erythermalgia, who experience sensations of burning pain in response to mild stimuli such as warming. And transgenic mice lacking Nav1.7 in their pain-sensing neurons have a reduced response to certain painful stimuli.

This new study, from an interdisciplinary team led by clinical geneticist Geoff Woods at the University of Cambridge, shows that loss-of-function mutations affecting this particular sodium channel completely block the detection of any form of physical pain. Loss of Nav1.7 is strikingly specific for pain – perceptions of touch, warmth, tickling and pressure are all unaffected.

Even though pain receptors contain many related sodium channels, none can compensate for the loss of Nav1.7. This sodium channel is thus a potentially important target for new pain-killing agents.

Image credit: Chris Nurse

External links

• Cox JJ et al. An SCN9A channelopathy causes congenital inability to experience pain. Nature 2006;444(7121):894–8.