Australasian Science: Australia's authority on science since 1938

Chronic Pain Relief Gets Legs

By Stephen Luntz

A molecule in the venom of certain centipedes could be used as a powerful pain reliever without the side-effects associated with the drugs currently available.

Humans have nine closely related sodium channels for cell signalling. Of these, Nav1.7 acts “like an amplifier for all pain signals,” according to Prof Glen King of the University of Queensland’s Institute of Molecular Bioscience.

“There are many different pathways by which pain can reach the brain, but the beauty of Nav1.7 is that it sits above everything else, and without it signals never get to the point where they can reach the brain – just as without an amplifier vibrations from different strings on an electric guitar never get heard.”

A molecule that blocks Nav1.7 would provide pain relief to millions of chronic sufferers. By interfering with an ion channel rather than a receptor, as opiates do, it’s thought that tolerance should not build up and require ever-larger doses. Moreover, since Nav1.7 does not involve the reward pathways triggered by opiates, addiction should be less of a concern.

The obstacle to the use of Nav1.7-blocking molecules has been that the related pathways are so important. “Nav1.5 is essential to the functioning of the heart, and if you block Nav1.4 you can paralyse people,” King says. Most molecules that interfere with a Nav1 channel also affect at least some of the others.

Insects have just one sodium channel, and the species that prey on them often use poisons to paralyse their meals. King says his team has examined the venoms of many arthropod species in the hope of finding one that was close enough to Nav1.7 that it could be modified to produce a harmless drug.

To their surprise, the team found that modification was not required because the Chinese red-headed centipede’s venom blocks Nav1.7 while appearing to have no effect at all on the other sodium channels. Mice injected with the molecule at ten times the analgesic dose suffer no consequences to heart rate, swimming capacity or blood pressure.

One obstacle is that the molecule is small and is cleared by the kidneys within 4 hours – an undesirably short period for sufferers or chronic pain. However, King says this could be overcome.