The stinging tree’s ouch

Australia is out to get you. If it’s not the snakes, it’s the spiders. If it’s not the spiders, it’s the sharks. If it’s not the sharks – it’s the trees.

Gympie-Gympie, or the stinging tree (Dendrocnide moroides), grows in northern New South Wales but is most commonly seen from Gympie in southern Queensland to Cape York Peninsula. Once you encounter it, you’ll never forget it. Entomologist Marina Hurley once described it as “the worst kind of pain you can imagine – like being burnt with hot acid and electrocuted at the same time.” 

Now scientists at the University of Queensland have been able to piece together just why the tree’s sting is so painful. In new research published in the journal Science Advances, they found that it has a previously unknown class of peptides in its venom, which not only causes the intense pain but also prevents neurons from inactivating – meaning that pain comes strong, and long.

The Gympie-Gympie’s leaves and stems have stinging hairs that break off and inject venom into anyone that brushes against them. Like Hurley, those envenomated can expect extreme pain that typically lasts several hours. But it can persist for days or weeks, occasionally requiring hospitalisation.

“Like other stinging plants such as nettles, the giant stinging tree is covered in needle-like appendages called trichomes that are around five millimetres in length – the trichomes look like fine hairs, but actually act like hypodermic needles that inject toxins when they make contact with skin,” says Irina Vetter, a member of the research team.

After extracting the venom from the plant, the researchers identified a range of peptides similar to spider and cone-snail venom toxins. They’ve named the new class of peptides “gympietides.”

“Nettle stings are due to small molecules like histamine,” says University of Adelaide toxicologist Ian Musgrave, who wasn’t involved in the research. 

“The Gympie-Gympie is not just a stinging nettle on steroids, but has developed an armoury of small proteins unique to it to give their sting an added punch.”

The gympietides’ structure is what’s known as an inhibitory cystine knot motif, says Musgrave. And, surprisingly, the same structure is found in several animal venoms.

“The evolution of animal venoms shows that many originally non-venom proteins can be pressed into service as venoms,” says Musgrave. “It is likely a previously innocuous inhibitory cystine knot protein has been pressed into service as a toxin through evolution.”

The cystine knot seems to directly activate pain-sensing neurons. However, their party piece is how they cause prolonged pain. According to the findings, they also delay inactivation of sodium channels on the neurons. 

These channels, which, as the name suggests, allows sodium to pass through the neuron’s membrane, are an important part of neuron activation. Open, they allow action potentials to be generated in the neuron, and activate signal transmission – in other words, the neuron is active. Inactivating the sodium channel prevents action potential generation. So essentially, the toxin prevents the neurons from “turning off”, and they keep transmitting pain signals.

“By a combination of pharmacological manipulation and gene knockout experiments the voltage-gated sodium channels of these pain sensing nerves, which are crucial for nerve activation, were shown to be the target for the gympietides,” says Musgrave. 

“The peptides effects were long lasting and were unable to be reversed, consistent with many bushwalker’s experience.”

And while UK chemical weapons researchers have reportedly previously investigated stinging tree venom as a potential bioweapon, it’s more likely these results will have beneficial outcomes. 

“The research by Gilding and colleagues is an excellent exploration of a unique protein plant toxin,” says Musgrave. “This will be a springboard to further fascinating research into the evolution of venoms, and hopefully for long suffering bushwalkers, an eventual antitoxin.”