Hot, hot, hot: peppers and spiders reach same pain receptor.

The burn of hot peppers and the searing pain of a spider bite may have a common cause. New research suggests that molecules in hot peppers and in a certain spider's venom target the same receptor on nerve cells.

Several years ago, scientists identified a channel on neurons that's opened by capsaicin, the molecule responsible for peppers' burn. Follow-up research showed that this channel is a member of a family of cell-surface receptors that sense both chemicals and temperature. When these channels are activated, ions flood into nerve cells and cause them to fire.

Although scientists have already studied components of spider venom that cause shock, paralysis, and death, little is known about the molecules that cause the pain. David Julius of the University of California, San Francisco and his colleagues wondered whether pain-inducing venom ingredients might activate the dual-purpose cell-surface channels.

The team purchased venoms collected from a variety of spider, scorpion, and snail species known to deliver painful bites. The researchers diluted the venoms and added them to dishes containing human-kidney cells that had been genetically altered to carry various types of channels.

Only the venom of one West Indian tarantula species, Psalmopoeus cambridgei, sent a flood of ions into cells that sported the same receptor that's sent by capsaicin. When the scientists broke down that venom, they c identified three component molecules c responsible for the rush of ions.

To confirm that these molecules opened the capsaicin-responsive channel, the researchers added each compound separately to dishes containing nerve cells from normal mice or from mice engineered to be missing just that channel. The team found that ions entered only the cells from normal mice. Furthermore, only animals with the capsaicin-responsive channel appeared to feel pain in response to any of the molecules.

The team reports its results in the Nov. 9 Nature.

Julius notes that because triggering the receptor produces such strong pain sensations, it's not surprising that organisms as distantly related as pepper plants and tarantulas use the same defensive mechanism.

"Different organisms have figured out how to tap this site as a way of telling predators, 'You won't be comfortable if you mess with me,'" he says.

Michael Caterina, who studies this family of dual-purpose cell-surface channels at Johns Hopkins University School of Medicine in Baltimore, notes that spider venom could eventually become a powerful tool for researchers to use in investigating channels active in several types of chronic pain.

"Anything that helps us understand how these channels are activated will facilitate [development of] drugs that block these channels," he says.