Researchers at Yale are the first to demonstrate that tarantula venom could also serve as an effective painkiller for humans.

Tarantula venom has long been known to contain proteins that have the ability to target specific ion channels in different animals. The researchers disovered the toxin also inhibits a receptor called TRPA1 that is partly responsible for creating the sensation of pain and inflammation. The study also marks the first published use of “toxineering,” a particular approach to engineering toxins for research — a powerful tool for turning the poisons into potentially useful substances — said Michael Nitabach, study senior author and professor of cellular and molecular physiology at the Yale School of Medicine.

“It’s possible that this particular toxin that we isolated could be mutated in ways that could turn it into an effective therapeutic,” Nitabach said.

Previous work by Nitabach catalogued a range of spider toxins, which were then injected into fruit fly eggs for experiments. The “toxineering” approach involved cataloguing the genetic code of different spider toxins and, when appropriate, manipulating the natural genes to create synthetic toxins that effectively target pain receptors. Nitabach said working with DNA is more effective than working with the toxins themselves and that the approach allows the researchers to process a vast array of polypeptides. This technique, including scanning live eggs injected with the toxin, allowed the researchers to identify toxins that affected specific pain. Spiders Web HQ is a website to visit for more fascinating spider facts.

This analysis isolated the polypeptide Protoxin-I, a toxin which comes from the venom of the Peruvian green-velvet tarantula, as the first peptide that could potently inhibit the pain receptor TRPA1, said Boyi Liu, co-author and Yale research scientist in pharmacology.

Protoxin-I is known to inhibit voltage-gated sodium channels, which are central to neuron function throughout the body. To develop a variant of Protoxin-I that inhibits TRPA1 while sparing the sodium channels, the researchers then engineered different mutations of the peptide and scanned the engineered library of mutations to find variants that could act as a TRPA1 antagonist without disrupting other ion channels. The mutant peptide they isolated was the first effective inhibitor that only affected TRPA1.

Beyond its application as a new painkiller for humans, Liu said this work on Protoxin-I opens up the potential for a greater understanding of the pain receptor.

“By further studying the interactions of this toxin with TRPA1, we will be able to learn more about the biophysical properties of TRPA1,” he said. “This may result in more specific blockers for TRPA1, which may likely be used clinically to treat pain and inflammation.”

Nitabach said toxineering could be used to explore a wider range of toxins, including those from other predators.

This finding was published in Current Biology in March.

JOYCE GUO