New Techniques Get At Pain Where It Hurts

From the WebMD Archives

Nov. 8, 2000 -- Thanks to modern biotechnology, the information superhighway may offer safer, more effective treatments for pain control and neurological diseases.

This information superhighway is not the Internet, but rather a sci-fi sounding nerve function called axonal transport, which allows communication between nerves by moving molecules from one end of the nerve to the other, over distances as long as four feet.

"Using the nerve itself as a conduit is the first true 21st century drug treatment," researcher Aaron Filler, MD, PhD, an assistant professor of neurosurgery at the University of California, Los Angeles, tells WebMD. "No one has realized the therapeutic possibilities until now."

Delivering drug molecules directly to pain-sensitive nerves allows more complete, longer-lasting relief with fewer side effects. Filler's research and other novel approaches to pain control were unveiled this week at the Society for Neuroscience's annual meeting in New Orleans.

"There's a lot of excitement about this among neuroscientists," Filler says. "It's like the discovery of Post-It Notes -- how do you put together old technology to do something new?"

A painkiller taken by mouth or even injected into the veins faces a perilous journey. Before reaching its intended target, it may be broken down by substances in the gut or liver, then flushed out by the kidney. To reach the brain or spinal cord, drugs must cross a roadblock called the blood-brain barrier. And drugs traveling in the bloodstream also reach other organs, causing unwanted side effects such as sleepiness, nausea, and even breathing problems.

Filler's research bypasses these problems by using axonal transport to carry drugs along the nerve to where they are needed most -- the spinal cord or brain, depending on the problem being treated. To safely convey drugs within the nerve, his group has designed a special molecule called an axonal transport facilitator that carries about 100 molecules of the drug being used. Like passengers on a bus, drug molecules can get off at different stops along the nerve or take the whole trip to the nerve cell body, where they provide long-lasting pain relief.


"Because it's released directly to where it's needed, you can use as little as 1/10,000th of the dose that would be needed by other routes," Filler says.

In animals, Filler showed that a single injection into a painful area of 1/300th of the usual dosage of a drug bound to the facilitator reduced evidence of pain by 50%, with pain relief lasting up to four days. Yet the drug alone, without the facilitator, had no effect on pain.

"This is not only a clever idea but a well-done study," John A. Jane Sr., MD, PhD, tells WebMD. "In humans, this approach might eventually be applicable to [painful nerve conditions] or cancer pain." Jane, who is professor and chair of neurosurgery at the University of Virginia Health System in Charlottesville, was not involved in the study.

Theoretically, by using a facilitator to deliver anesthetic to people during surgery, a single shot of 1/1,000th of the usual dose could give several days of pain control after surgery, while avoiding side effects that could lengthen hospital stay. By using this technique with well-known drugs, "we could be optimistic about safety issues," Filler adds.

"This is a very flexible program to solve many different types of problems," says Filler. Using a pain medication on pain-sensitive nerves could relieve pain in conditions like shingles or diabetes, while injecting it into muscles could relieve muscle spasm in multiple sclerosis or spinal cord injury. Human studies are scheduled to begin in early 2002.

Drugs that might be effective in Alzheimer's disease or other brain diseases could be sprayed into the nose, where nerve cells lining the nose could carry them directly to the brain. Many drugs that were ineffective when given by mouth or into veins may prove to be useful once they reach their intended target.

Another approach to pain control is to transplant cells that make serotonin, a brain chemical thought to relieve pain, directly into the spinal cord. Acting as biological mini-pumps, they could deliver continuous pain relief while minimizing side effects.


"If this works in humans, it would be [as effective as] a kidney transplant for someone in kidney failure -- it would substitute for the loss of normal regulatory systems influencing pain," Bruce Nicholson, MD, director of pain management at Lehigh Valley Hospital in Allentown, Pa., tells WebMD. "This could be of great benefit for long-term pain control without medications," says Nicholson, who was not involved in the study.

In animals with spinal cord injuries, researchers at the University of Texas Medical Branch in Galveston and the Miami Project to Cure Paralysis found that these transplanted cells improved movement and decreased evidence of pain. However, there are many issues that must still be addressed before testing this approach in humans.

SynGenix, Ltd. of Cambridge, England, partly funded the axonal transport facilitator research. Filler is a co-founder, consultant, and significant shareholder in SynGenix, which holds the rights to ProVector, this axonal transport system.

WebMD Health News Reviewed by Jacqueline Brooks, MBBCH, MRCPsych
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