Capsaicin Drug for Chonic Severe Pain
Resiniferatoxin (RTX) Drug for Chonic Severe Pain
NIH Awards $1.4M to Study of Ultra-Potent Capsaicin Drug for Chonic Severe Pain, Alternative to Morphine
November 5, 2009
A pharmacologist at Southern Illinois University School of Medicine, Springfield, has received a $1.4 million grant from the National Institute of Drug Abuse to study a new chronic pain treatment.
Louis Premkumar, PhD, associate professor of pharmacology, is the principal investigator for the project. The research will study a new drug, Resiniferatoxin (RTX), as a potential treatment for chronic, debilitating, terminal pain in patients such as those with bone cancer or large mass abdominal cancer where other drugs are not effective. (Currently the only treatment for human patients with such chronic pain is morphine, which has severe side effects.)
RTX is an ultra-potent capsaicin compound - a form of the irritant that gives chili peppers their ‘fire’. It is extracted from the sap of a highly irritating, cactus-like plant native to Morocco, and is some 1,000 times more potent than the capsaicin in chilis.
Chili-derived capsaicin is used in topical preparations, for example, to temporarily numb neurons in a pain-messaging system responsible for heat-related, inflammatory pain - while RTX ‘shatters’ and kills these cells.
The first experiments with RTX involved dogs suffering from painful bone cancer. After an RTX injection in the spinal cord they were able to move and play again, apparently pain free, for weeks to months. Because RTX burns before deadening pain, injections require general anesthesia.
Sources: • Southern Illinois University School of Medicine news release, Nov 3, 2009
• “Fiery pepper may hold key to easing pain,” AP, 2008, by Lauran Neergaard. http://www.seattlepi.com/health/255908_pain17.html
• Wikipedia - Resiniferatoxin http://en.wikipedia.org/wiki/Resiniferatoxin
Fiery pepper may hold key to easing pain
By LAURAN NEERGAARD
THE ASSOCIATED PRESS
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 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 as if it's burning a hole in your tongue -- yes, one researcher tasted it -- relieve pain, too?
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," explained 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 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 percent 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, said 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 predicted.
Optimistic, the NIH is seeking 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," Iadarola pledged
SIU prof gets $1.4 million to study pain treatment
Drugs and Medicines
SPRINGFIELD, Ill. - An Illinois researcher has received a million-dollar federal grant to study a potential new treatment for chronic, debilitating pain.
The experimental drug comes from a cactus-like plant and is similar to the active ingredient in hot peppers.
Pharamacology Professor Louis Premkumar was awarded the grant from the National Institute on Drug Abuse. He'll be investigating the drug in his lab at Southern Illinois University's medical school in Springfield.
The drug is called Resiniferatoxin (reh-sin-ih-FEHR-oh-tox-in). It's injected directly into the spinal cord. Researchers hope it could be an alternative to morphine, which has severe side effects.