Plant could hold secret for new pain medication By LAURAN NEERGAARD, The Associated Press January 17, 2006 - seattletimes.com
WASHINGTON — The dog hopped on three legs, pain from bone cancer so bad that he wouldn't let his afflicted fourth paw touch the floor. His owner was bracing for euthanasia when scientists offered a novel experiment: They injected a fiery sap from a Moroccan plant into Scooter's spinal column — and the dog frolicked on all fours again for several months.
The chemical destroyed nerve cells that sensed pain from Scooter's cancer, not helping the tumor but apparently making him no longer really feel it.
The dramatic effect in dogs has researchers from the National Institutes of Health preparing to test the chemical in people whose pain from advanced cancer is unrelieved by even the strongest narcotics.
The first human study could begin by next year, at the NIH's Bethesda, Md., hospital. A second study in dogs is slated for this summer at the University of Pennsylvania.
If the research pans out, it might one day offer doctors a desperately needed new approach to attack intractable pain. And it's from an unlikely source, a more potent cousin of the chemical that makes chili peppers hot.
Why would a substance that feels as if it's burning a hole in your tongue — yes, one researcher tasted it — relieve pain?
This fiery chemical — called resiniferatoxin (RTX) — can poison certain nerve cells that control a type of heat-related, inflammatory pain, apparently eliminating one of the body's pain-sensing systems. Yet it doesn't seem to harm other nerves that sense, for example, the sharp pain from stepping on a tack.
"The beauty of this is it just selectively targets," said Dr. Andrew Mannes, an NIH anesthesiologist who specializes in pain management.
The discovery led government scientists to scour the hillsides of Morocco for the cactuslike plant and take the unusual step of essentially manufacturing an experimental drug from its sap.
Narcotics called opioids, such as morphine, are the mainstay of treatment for pain from late-stage cancer. But between 5 and 15 percent of patients — anywhere from 40,000 to 100,000 Americans a year, Mannes estimates — don't get relief. There's an urgent quest for novel options. Michael Iadarola, a pharmacologist with the NIH's National Institute of Dental and Craniofacial Research, was studying how nerve endings move the pain message up to the brain. For pain caused by cancer, one route is through certain nerve cells, or neurons, in the spinal region that also carry a specific receptor controlling calcium flow. Too much calcium kills cells.
Capsaicin, the chemical from chili peppers, stimulates this receptor to let in extra calcium. But RTX proved 1,000 times more potent. Touched to neurons with this receptor, RTX spurs a flood of calcium that shatters the cells' walls and quickly kills them.
Getting RTX to just the right cells requires an injection similar to the pain-relieving epidurals that women receive during childbirth, but deeper into the spinal column. RTX temporarily burns before it deadens pain, so the injection requires general anesthesia.
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