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Blocking Pain at its Source

Research for new painkiller finds inspiration in chili peppers

Inspired by chili peppers, researchers are working toward a painkiller that could stop the brain from registering the presence of pain.
Inspired by chili peppers, researchers are working toward a painkiller that could stop the brain from registering the presence of pain.

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Anyone who has ever had to recover from surgery or a serious injury was probably grateful for the powerful narcotics doctors prescribed to help ease the pain. But all these medications do is dull the brain's perception of pain.

Your brain registers pain through neurons, special cells that wind through the body. When you touch boiling water, for example, get a cut, or even exercise too much, a special receptor on the neuron is activated, sending a signal to the brain — that hurts!.

This much scientists knew. However, they were not clear on how that receptor was activated when this kind of painful event occurred.

The chili pepper model

University of Texas researcher Kenneth Hargreaves says they got an important clue from chili peppers.

He explains that, while people think of the capsaicin from chili peppers as a spice, "it is actually a selective drug. It really produces its effects primarily by just activating the so-called capsaicin receptor."

When we eat chili peppers, we feel a burning sensation. That feeling is caused by the capsaicin molecules in the peppers activating the capsaicin receptors on our tongue — the more capsaicin, the hotter the pepper.

In the course of an entirely different experiment, Hargreaves and his team of researchers discovered that the skin produces its own capsaicin-like molecules, in response to pain.

"We took isolated skin biopsies from laboratory mice, exposed those isolated skin biopsies to temperatures of 43 degrees or 48 degrees, and then we looked at what was being released from the skin under those conditions." Heat typically becomes painful at about 47 degrees Celsius.

When the skin samples were heated to 48 degrees, they produced this capsaicin-like molecule into a solution. Then, Hargreaves says, the researchers applied the solution to mice neurons; some with the capsaicin-receptor and some that had been genetically modified to eliminate that receptor.

"The ability of these substances to activate pain neurons was totally dependent upon capsaicin receptor," says Hargreaves.

A new approach to treating pain

Hargreaves says this is a huge discovery, one that could fundamentally change how doctors treat pain. "Now that we have discovered the endogenous capsaicin molecules, for the first time, we can block their synthesis and therefore we can treat pain at its cause."

Narcotics, the most powerful drugs currently available to fight pain, simply dull the brain's perception of it. But if a medication can block the capsaicin-like molecule from reaching the neuron, it could stop the brain from ever registering there was any pain to begin with.

Hargreaves and his team are already in the process of developing two classes of drugs that do just that. One would stop the body from producing the capsaicin molecule. Another would soak it up, before it reached the receptor on the neuron.

And crucially, these drugs do not seem to have the same potential to become addictive, the way narcotics do. Hargreaves says the first class of drugs could begin clinical tests in humans within the next six months.

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