Finding the perfect painkiller is difficult. To stop pain, you have to stop nerves from working – the key is to turn off the right nerves while leaving others alone. To do that, you have to find the perfect molecular target. For Glenn King of the University of Queensland in Brisbane, Australia, that target is a sodium ion channel called NaV1.7.
King calls it “a really gorgeous target” because people born without that channel don’t experience any pain. “So the expectation is that if you can deal with a drug that very selectively blocks that channel, you’ll kill all pain. For people who suffer from chronic pain, this would be a godsend.”
Current painkillers are very general. Morphine reduces the transmission of pain signals by dulling nerves throughout the body, including non-target ones (hence the sluggishness that often accompanies the drug). It also alters how your brain processes pain, which can also make it addictive. Meanwhile, over-the-counter medications like ibuprofen don’t actually block pain – they only reduce the activity of enzymes in the body, which can reduce certain kinds of pain but not others.
If a molecule blocked NaV1.7 channels and only NaV1.7 channels, it could have all the benefits of morphine with none of the addictive side-effects. However, there are eight other types of sodium channel, “so getting it to be really selective has proved to be really difficult,” says King.
Now, however, he has a place to start: μ-SLPTX-Ssm6a, or Ssm6a for short – a peptide from centipede venom. So far, research has found Ssm6a to target the right ion channels with a high selectivity not seen in other painkilling compounds. It is more potent than morphine in rats. While it’s still in the early stages of development, it’s possible that Ssm6a or a derivative of it will be making its way through clinical trials in the future.
The interesting thing about Ssm6a is that it serves a very different purpose in nature. For the centipede’s prey, insects, Ssm6a isn’t a painkiller: it’s a potent paralytic.
“In contrast to humans, insects express only a single NaV channel,” write King and his coauthors in a paper published in Proceedings of the National Academy of Sciences in 2013. These channels are found throughout the body, so when an insect has its NaV channel shut down, its whole body is shut down. “Although it might seem counterintuitive that a venom peptide used for predation could be a useful therapeutic, the significant differences in primary structure and tissue distribution between insect and human ion channels makes this possible.”