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New treatments for chronic pain focus on blocking nerve signals

WASHINGTON—Scientists are developing new ways to relieve chronic pain, the long-lasting suffering that afflicts millions of people worldwide.

They're learning how to block the nerve signals that carry pain messages to the brain without interfering with normal body functions, as earlier treatments often did.

Unlike acute pain—say from a cut, burn or broken bone—which comes and goes quickly, chronic pain can drag on for months, years, even a lifetime.

The problem affects "vast populations of people," said Dr. Andrew Mannes, an anesthesiologist at the National Institute of Dental and Craniofacial Research in Bethesda, Md. "People are not able to get out of bed and get to work. Billions of dollars are involved."

Migraine headaches, for example, make 28 million Americans miserable. "It's the number one reason for people being absent from work," Mannes said.

Short-term, acute pain can be useful, researchers said. It's an alarm system that tells you to pull your hand away from a hot stove or avoid walking on a broken ankle until it heals. In contrast, chronic pain—from cancer, arthritis or lower back problems—serves no beneficial purpose and resists standard treatments.

"Even if we do everything right, there are still people who have unrelieved pain," Mannes said. "That's why we're trying to come up with new treatments for those cases that just don't respond."

To meet the challenge of severe chronic pain, two novel therapies are being developed at the dental and craniofacial institute, a branch of the National Institutes of Health. Both involve breaking the circuit that connects pain nerves to the brain through the spine.

One method uses a poisonous substance called RTX (short for resiniferatoxin) derived from a cactuslike plant in Morocco. Inserted into the sheath surrounding the spine, RTX kills certain specialized clusters of neurons—nerve cells—that help transmit painful sensations to the brain.

"RTX deletes only the sensory neurons," said Michael Iadarola, a pain expert at the institute. Other nerves, such as those that control touch, motion and balance, are unaffected.

Iadarola has used RTX successfully to relieve pain in dogs that have severe bone cancer and is seeking approval to test the technique in humans next year.

"We hope the response will be as nice as we saw in dogs," he said.

The other technique uses a toxic molecule called SP-PE35 to selectively remove the outer, pain-sensing layer of the spinal cord while leaving intact the nerves that control muscles, breathing and other organs.

"We shave neurons off the top of the spinal cord," Iadarola said. "Some have referred to the technique as using a molecular scalpel."

Researchers plan to test the new process in dogs and eventually in humans. It already has been shown to work in laboratory rats, who feel no pain when their tails are pinched.

Currently, doctors have no way of selectively eliminating nerve cells that are involved in chronic pain. Standard treatments, such as morphine or codeine, don't provide universal relief and may cause serious side effects.

Other scientists are working on the genetics of pain. Clifford Woolf, an anesthesiologist at Harvard Medical School in Boston, has identified 137 genes that play a role in pain.

"Each of them is a potential drug target," said Jeffrey Mogil, a neuroscientist at McGill University in Montreal. "There may be thousands of genes involved in pain."

One experimental drug, Mogil said, works only in red-haired women, not in blondes, brunettes or men. No one knows why it's so choosy.

The National Institutes of Health has a budget of $237 million for pain research this year, up from $199 million four years ago. It's formed a consortium of pain researchers at http://painconsortium.nih.gov.

"We've come a long way," Mogil said.

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For more information, visit the American Pain Society's Web site, at www.ampainsoc.org/member/sigsites/paingen-founders.htm.

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(c) 2005, Knight Ridder/Tribune Information Services.

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