updated 1/16/2006 2:04:27 PM ET 2006-01-16T19:04:27

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.

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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 pain-ridden dogs is slated for this summer at the University of Pennsylvania.

If the research pans out, it might one day offer doctors, and veterinarians, 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 chile peppers hot.

Why would a substance that feels like it’s burning a hole in your tongue — yes, one researcher tasted it — relieve pain, too?

Selective targets
This fiery chemical, called resiniferatoxin or 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, say, the sharp pain from stepping on a tack.

“The beauty of this is it just selectively targets,” explains Dr. Andrew Mannes, an NIH anesthesiologist who specializes in pain management.

“If you live a long time, you need all your pain systems. There are people on morphine drips with really no other option. (Eliminating one) seems like a good trade.”

The discovery led government scientists to scour the hillsides of Morocco for the cactus-like 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 NIH’s National Institute of Dental and Craniofacial Research, was studying how nerve endings in the skin and other body parts move the “I’m hurting” message up to the brain. For cancer-caused pain, 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, that chile pepper chemical, stimulates this so-called vanilloid receptor to let in extra calcium. But RTX, from a plant long known to cause skin rashes and other irritation, proved 1,000 times more potent. Touched to vanilloid-bearing neurons, 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. Complicating matters, RTX temporarily burns before it deadens pain, so the injection requires general anesthesia.

RTX seemed to work in rats, but Iadarola needed more evidence.

Enter dogs, who get many human diseases and often react to human medicines just like people do, notes Dr. Dorothy Brown, a Penn veterinary surgeon.

She injected RTX into 18 dogs with untreatable bone cancer pain. The next day, the dogs once again put weight on their diseased legs. While all eventually were euthanized because of worsening cancer, their owners reported weeks, sometimes months, of playing and activity.

The main side effect so far: The dogs wake up panting heavily for a few hours. Presumably, they’re flushed like people get after eating hot peppers. “When this is injected into people, they are going to sweat like a bear,” until the RTX finishes working, Brown predicts.

Optimistic, the NIH is hunting a pharmaceutical company to take over developing the experimental drug. That may be a challenge: This would be a small market. Still, the Food and Drug Administration already has designated RTX a potential orphan drug, easing research requirements.

Regardless of industry interest, if RTX works in people like it seems to in dogs, “we’ll go the distance ... and make it a medicine,” pledges Iadarola.

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