As painful as a spider bite may feel, the molecular mechanism that underlies how venom produces that sensation isn't well understood. Little is known about the molecular channels through which ions flow across the membrane of sensory neurons and thereby trigger a firing of electrical signals perceived as pain. Now researchers examining arachnid venom may have discovered a new tool to probe deeper into how ion channels work to produce pain.

David Julius and his colleagues at the University of California, San Francisco, screened 22 different species of spiders and scorpions in search of molecules that activate sensory neurons and produce pain sensation. The researchers identified and purified three molecules in the venom of a West Indian tarantula species, Psalmopoeus cambridgei, that do so. When the researchers injected the toxins into the paws of mice, their limbs became inflamed and the animals reacted by licking them and flinching. Mice genetically engineered not to express the receptor, however, did not react when the toxin was administered, according to the study appearing in the November 9 issue of Nature.

The peptides isolated from the tarantula species target the same receptor as capsaicin, the fiery compound in hot chili peppers. The pepper molecule and the tarantula toxins activate the same channel but in different ways: capsaicin binds the receptor from inside the cell whereas the tarantula peptides target the receptor from the outside. "One can achieve the same, or very similar, molecular consequences by tickling this channel in two different places," says Mike Catarina, a biochemist at Johns Hopkins University. This unusual situation may prove a powerful laboratory tool, he adds. Because the tarantula toxins target the outside of sensory neurons, the peptides could be used to study neurons without destroying them. And unlike similar peptides that inhibit other ion channels, this new class of "vanillotoxins" excites channels when it binds to the receptors. This characteristic may aid in developing analgesic drugs based on channel structure.

"The plant and the spider, through evolution, have come up with the same general molecular strategy for averting predators by activating this same receptor," Julius says. Capsaicin helps the pepper to scare off mammals but does not affect birds that could spread the pepper seeds. But the tarantula toxins identified in the study activate both bird and mammal channels, suggesting that spiders evolved a toxin to defend themselves against many different predators. Sensory systems are a great way to understand how organisms interact, Julius says. "They define how we perceive our world."