Burning away the pain

When Dottie Brown was in high school she worked at a local veterinary practice, learning valuable real-world lessons about her career of choice.

Penn Associate Professor of Surgery Dottie Brown

Dogs such as Ursula can’t help but love Penn Associate Professor of Surgery Dottie Brown, who has been working on finding new ways to measure and treat their pain.

Photo credit: Candace di Carlo

But even as a teenager, Brown sensed something odd about the way the veterinarians of the day treated—or maybe more accurately, didn't treat—their patients' pain.

“It used to be that animals very rarely got post-surgical pain management,” Brown says. “The rationale was, ‘Well, we just fixed the broken bone and we don’t want the dog to move around, so if we don’t give them pain meds they won’t move and that will be good.’ And I’d have to say that rationale, 20 years ago, was not all that uncommon.”

Today, Brown is at the forefront of a push in the veterinary world to give dogs access to the same pain relief that humans have become accustomed to. As an associate professor of surgery at the Ryan Veterinary Hospital and an active researcher on animal pain management, Brown is working to find new ways to help dogs stricken with such diseases as cancer or arthritis live pain-free lives. Recently, Brown's expertise drew her into a study that is revealing some unusual and unexpected pain-management properties of a fiery compound called resiniferatoxin (RTX), a red-hot sap produced by a Moroccan cousin of the chili pepper plant.

Researchers at the National Institutes of Health working to better understand pain in human beings discovered that, in cancer patients, pain messages were sent to the brain by a certain class of nerve cells in the spine. But these nerve cells, the researchers found, could be killed if infused with calcium—and once killed, the pain messages could be stopped.

That's where RTX comes in. When the chemical—about 1,000 times more potent than the capsaicin that gives chili peppers their kick—makes contact with the pain-transmitted nerve cells, it spurs a rush of calcium into the cells, destroying them and providing relief from cancer's life-depleting pain.“When we give [RTX] in the spinal fluid in the spinal cord, those [pain] cells are permanently deleted, and they can't send the signal,” Brown says.

The NIH team found RTX seemed to work on lab rats, but needed more evidence to support their claim. And because humans and dogs are so similar, medically speaking, they turned to Brown, whose work had put her in contact with dogs suffering from severe cancer pain. Brown, in turn, sought out dogs that might make good case studies. She chose a group that had been stricken with cancer, and were so wracked with pain they were unable to put weight on their limbs. Some had given up on playing completely.

But after taking injections of RTX, those same dogs were able to run and jump almost as if they felt no pain at all. The cancer persisted—and eventually proved fatal—but owners reported weeks or months of happy times after RTX treatment. “These were dogs who didn’t really want to walk around anymore. The owners were basically at the point of considering euthanasia,” Brown says. “Some of those who were on other pain meds coming in actually discontinued those afterward.”

The initial trial was such a great success that Brown will conduct another, more thorough study this summer. Meanwhile, the NIH team is pushing to begin testing RTX on humans soon.
Brown says it's unlikely RTX will ever replace such pain-management standbys as morphine—RTX can only be delivered by spinal injection and patients must be anesthetized during application—but she says it could eventually provide another tool in doctors' and veterinarians' ongoing fight to relieve pain. Besides, Brown says, it was not too long ago that the thought of injecting a toxin into somebody's face would raise some eyebrows: But that's precisely what users of Botox—which, like RTX, is a neurotoxin—are doing.

“This whole field is pretty new," Brown says. "RTX would fall under the group of neurotoxins—drugs that have a really toxic effect on nerves. But it's only recently that you're beginning to realize you can use those same properties, but in a good way.”

Originally published on March 16, 2006