Pain in the ants. Ant venom a key to unlocking chronic pain.

If you’ve had the unfortunate experience of being bitten by a Green Ant (Rhytidoponera metallica) in Australia, you’ll understand the long-lasting pain and irritation inflicted by such a tiny creature. The majority of ant species produce venom and some have characteristic and exceptionally painful stings. The bullet ant (Paraponera clavata) of tropical Central and South America was rated as having the most painful insect sting in the world by the late Dr Justin Schmidt, an American entomologist who created a pain index of stinging insects. Stings of the bullet ant can cause uncontrollable trembling and immediate intense local pain that can last for up to 12 hours; 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. 

In studying multiple ant species with long-lasting pain effects, CIPPS researchers Dr Andrew Walker, Chief Investigator Glenn King, Associate Investigator Tina Schroeder (Genentech) and collaborators, have shown for the first time that some of the world’s most painful ant stings release peptide toxins that target mammalian voltage-gated sodium (Nav) channels in nerve cells that are critical for sending pain signals.  

Sodium channels play a critical role in modulating pain signalling in mammals. Sodium channels are proteins which sit through the membrane bilayer of a cell and act like a gate to allow sodium ions to pass through.  When the balance of sodium ions inside a neuron is disrupted, there can be an explosion of electrical activity between the nerve cells when the channel is activated, or a complete disruption of nerve communication when the channel is inhibited. Normally, the sodium channels in pain-sensing neurons open only briefly in response to a stimulus. The team discovered that the ant peptide toxins, such as Ta3a, poneratoxin (Pc1a), Rm4a, and U3-MYTX-Mri1a (Mri1a), bind to sectors of the sodium channels at nano- and micromolar concentrations and cause them to open more easily and stay open and active for longer, which translates to a long-lasting pain signal. The peptide 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 biochemical tools to work with. 

Ants work collaboratively as a cohesive unit and have evolved defence mechanisms to not only survive, but to thrive in a world with much larger predators. Studying peptide neurotoxins to understand pain at a molecular level and research into how pain works can help develop new ways to treat it. The small but mighty ant might just hold another key to unlocking new therapies in the treatment of chronic pain.  

Reference: https://www.nature.com/articles/s41467-023-38839-1 

DOI: 10.1038/s41467-023-38839-1  

Paper: Ant venoms contain vertebrate-selective pain-causing sodium channel toxins 

Centre members involved: Glenn King (UQ), Andrew Walker (UQ), Sam Robinson (UQ), Tina Schroeder (Genentech)