Pain pathway targeted by a notorious Australian stinging tree

The researchers have identified a unique pain pathway targeted by a notorious Australian stinging tree and say it could point the way to new, non-opioid pain relief.

The research team have studied how toxins in the venom of the Gympie-Gympie tree cause intense pain that can last for weeks.

The senior author said the plant’s toxins - named gympietides in earlier work by the team - interact with nerves after being injected by fine needle-like hairs on the leaves.

“The gympietide toxin in the stinging tree has a similar structure to toxins produced by cone snails and spiders, but the similarity ends there,” the senior author said.

“This toxin causes pain in a way we’ve never seen before.”

Many toxins cause pain by binding directly to sodium channels in sensory nerve cells, but the the researchers have found the gympietide toxin needs assistance to bind.

“It requires a partner protein called TMEM233 to function and in the absence of TMEM233 the toxin has no effect,” the senior author said.

“This was an unexpected finding and the first time we’ve seen a toxin that requires a partner to impact sodium channels.”

The team is working to understand whether switching off this pain mechanism might lead to the development of new painkillers.

“The persistent pain the stinging tree toxins cause gives us hope that we can convert these compounds into new painkillers or anaesthetics which have long-lasting effects,” the author said.

“We are excited to uncover a new pain pathway that has the potential for us to develop new pain treatments without the side effects or dependency issues associated with conventional pain relief.”