‘World’s most painful insect sting’ found to target nerves in unique way

If you’ve been stung by an ant, you know how painful it can be. Australian researchers have found that some of the most painful ant stings are caused by nerve-targeting neurotoxins. But, unlike those found in snake and scorpion venom, ant toxins affect the body in a never-before-seen way. Their findings further our understanding of how pain works and how it might be treated.

Even though the majority of ant species produce venom and many produce a painful sting, little research has been done to explore the mechanisms that cause that pain. This is mostly due to the insects’ size, which makes collecting and analyzing their venom tricky. Researchers from the University of Queensland studied the Australian green ant and the South American bullet ant, both of which have stings that cause severe, long-lasting pain.

The green ant, or greenhead ant, is found throughout Australia, including urban and suburban areas. They like to nest beneath most grasses and usually go unnoticed until someone is stung, resulting in a sharp burning sensation within seconds. Bullet ants inhabit humid lowland rainforests in Central and South America. They got their name from the pain people experience when they’re stung by one, which compares to the pain of being shot. A bullet ant sting can also cause severe muscle contractions and burning. The late American entomologist Dr Justin Schmidt, who created a pain index of stinging insects, rated the bullet ant sting the most painful insect sting in the world.

"Bullet ant stings can be painful for up to 12 hours, and it's a deep drilling pain you feel in your bones with sweating and goosebumps, quite unlike the 10-minute impact of a typical bee sting," said Sam Robinson, lead author of the study. "We don't have bullet ants in Australia, but our green ant – or greenhead ant – can also cause long-lasting pain and many Australians will have experienced this."

Studies in the 1990s identified a poneratoxin – a paralyzing toxic peptide – in the bullet ant's venom, which affects sodium channels in the skeletal muscle fibers of frogs and rats. The feeling of pain is due to the action of sodium channels in the membranes of our sensory neurons (nerve cells). Put simply, sodium channels allow information from pain receptors in the peripheral nervous system to be conducted to the central nervous system, registering pain.

In the current study, the researchers wanted to identify the pain-causing agents in green and bullet ant neurotoxins by examining what was happening on a cellular and molecular level. They tested and analyzed the venom on the sensory neurons of mice, finding that the toxins specifically targeted the neurons’ sodium channels.

"We have shown that these ant venoms target our nerve cells that send pain signals," Robinson said. "Normally, the sodium channels in these sensory neurons open only briefly in response to a stimulus. We discovered that the ant toxins bind to the sodium channels and cause them to open more easily and stay open and active, which translates to a longer-lasting pain signal."

They found that the ants’ peptide toxins were structurally distinct from other sodium-channel-affecting toxins and that their mechanism of action is unique to the insect.

"These neurotoxins which target sodium channels are unique to ants; no one has found anything that looks or acts the same way, so now we have a new set of tools to work with," Robinson said.

Ants have been using neurotoxins to fend off predators since the age of the dinosaurs. The researchers say the new discovery is important for our understanding of how pain works and for developing new ways to treat it.

"We want to understand pain at a molecular level and toxins are fantastic tools to do this," said Robinson.

The study was published in the journal Nature Communications and the below explainer video was produced by the University of Queensland's Institute for Molecular Biology.

Source: University of Queensland