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Body's "heat messenger" offers new painkiller

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Reuters - Researchers have discovered the body's own "heat messenger," which helps nerves feel pain, and said on Monday they hope to use it to design a new, safer class of painkillers.

They found heat activates basic fatty acids similar to capsaicin, the compound that gives chili peppers their kick, and found two potential ways to block the sensation.

"For the first time we have the opportunity to try to block pain at its source," Dr. Kenneth Hargreaves of The University of Texas Health Science Center at San Antonio, who led the study, said in a telephone interview.

He said his team is now working to develop either a pill that people could take to block the effects of these natural "heat messengers," or engineered immune system proteins called monoclonal antibodies that could be infused to mop them up.

Such an approach should work on any kind of pain caused by inflammation, he said -- arthritis, cancer or injury. He is uncertain about its effects in other types of pain called neuropathies.

Most painkillers mask pain but do not affect its source. Narcotics or morphine are examples and are addictive and deadly. Non-steroidal anti-inflammatory drugs such as aspirin can help ease the inflammation that causes arthritis pain or a headache but have side-effects.

Aspirin can cause deadly bleeding, related drugs called COX-2 inhibitors sometimes cause heart problems, acetaminophen, also known as paracetamol, can damage the liver. None are highly effective.

Writing in the Journal of Clinical Investigation, Hargreaves and colleagues said they first looked for the basic cause of the pain and narrowed it down to the capsaicin receptor, a molecular doorway on nerve cells.

"The capsaicin receptor is like the master lock in our pain neurons," Hargreaves said.

"We have mice now with a genetic deletion of this master lock. Those without it show almost no pain from inflammation or cancer or burn injuries, so that we know that this receptor is critically important in terms of how the body responds to injury."

The capsaicin in red hot chili peppers unlocks this master lock, Hargreaves said. He wanted to find a way to block the keyhole, which is called transient potential vanilloid 1 or TRPV1.

Tests on mouse tissue showed heat did not directly activate pain neurons. Instead, in response to heat, cells create their own natural capsaicins called oxidized linoleic acid metabolites or OLAMs.

In a commentary on the findings, David Brown and Gayle Passmore, at University College London, called the newly discovered pain compound a "heat messenger."

Hargreaves said his team has some candidates for both a pill and an antibody but "I am not at liberty to discuss them." The university has a patent application for both potential routes.

While researchers can design drugs that will fit like a puzzle piece into a cell receptor, or screen libraries of existing compounds to see if one might work, Hargreaves said his team did neither.

"We did it the old fashioned, stupid way. We got lucky," he said.

"Our findings are truly exciting because they will offer physicians, dentists and patients more options in prescription pain medications. In addition, they may help circumvent the problem of addiction and dependency to pain medications, and will have the potential to benefit millions of people who suffer from chronic pain every day."

- Reuters

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