Hard Drinks

Hot pepper solution gives clue 
to new types of painkillers, reports Biplab Das

A German and American research team has recently cracked the mystery of the burning sensation that we experience after a bite of hot pepper. The study, published in a recent issue of Science, is also a potential precursor to the development of whole new group of painkillers. 

It was known that palate cells are excited by capsaicin, the active ingredient of chillies and peppers. But, scientists did not know the exact target site of capsaicin molecules. 

Scientists Michael Catarina, David Julias and Allan Basbaum, University of California, San Francisco, and Martin Koltzenburg, University of Wurzburg, Germany, found that the cell surfaces of the tongue contain a protein that acts as the receptor to capsaicin. They dubbed this receptor protein vanilloid receptor (VR1). 

After this initial breakthrough, they knocked the VR1 gene, which encodes for the receptor protein, in mice and noticed that the animals failed to develop capsaicin-induced pain. 

The researchers also observed that mice devoid of the VR1gene were less sensitive to high temperatures and other external factors that induce pain. "This shows that the receptor is not only an essential part of vanilloid sensitivity but also plays an important role in several other kinds of pain," says Julias in an article in Science. 

To confirm their observations, the scientists injected capsaicin into the hind paws of normal mice. They responded immediately by licking and shaking the paws. But, the genetically deficient mice, after the same procedure, remained immune to the effects. Moreover, their paws did not swell up like those of the normal mouse. 

As a follow-up, the normal mice were given a drink of capsaicin-laced water. After a sip, the rodents started rubbing their snouts and refused to have a further drink. "The mutant mice, however, kept drinking without any hesitation," says Caterina. They also didn't show any unease when their tails were dipped in hot water. 

"This does not mean that the mutant mice are bereft of any sensitivity but their responses are mellowed down to a great extent," says Caterina. 

In order to make their research foolproof, the team performed one last experiment. They spread mustard oil on the paws of the normal mice, resulting in inflammation and hypersensitivity to heat. When the mice lacking the VR1 gene received the same treatment, they did not show any of the above responses. However, they remained alert to touch-sensitive pain. 

They found that the acids produced by inflammation stirred neurons carrying VR1 receptors, resulting in pain and hypersensitivity. But, in mutated mice, the neurons did not possess the receptors and thus showed mild response to the acids. With this evidence in their hands, the researchers are now gearing up to develop VR1 blockers, which could lead to new pain-relieving drugs in the near future.