October 17, 1997

Researcher studying new way to ease chronic pain

Researcher studying new way to ease chronic pain

A drug that could help millions of chronic pain suffers lead more comfortable lives is currently being developed by a VUMC researcher.

The drug works by smuggling a plant-based poison into neurons controlling chronic pain. The poison is targeted only to kill these specific neurons, leaving intact the neurons responsible for normal pain sensation.

"I have seen patients with cancer who have severe pain that we have had to give so much narcotic that they could not function. This drug might end that method of pain management," said Dr. Ronald G. Wiley, professor of Neurology and Pharmacology and a clinical neurologist at the Veterans Administration Hospital.

"This is not the kind of treatment that would be used for a sprained ankle or a broken thumb. This is a method to be used when you know there is nothing you can do to make the pain go away and the goal is simply to make the patient comfortable."

A study outlining the mechanism of this agent is described in the October issue of Science magazine.

The neurons responsible for chronic pain are destroyed by a drug called saporin, which is smuggled into the cell using a neuropeptide that is taken up by pain-causing cells.

"Saporin is isolated from the seeds of the soapwort plant. It kills cells by destroying the ribosomes, which are responsible for protein synthesis," said Wiley.

With no way to enter the cell on its own, Wiley has developed a way to smuggle saporin into the cells by attaching it to a neuropeptide, called substance P, that is accepted only by spinal neurons which cause chronic pain.

When substance P is normally released into neurons it causes them to become hypersensitive to glutamate, a fast-acting neurotransmitter responsible for pain sensations.

"Substance P basically amplifies the signal so that even signals that would normally not cause pain instead cause a great deal of pain," said Wiley.

By destroying this select group of neurons that cause nagging pain, cancer patients, amputees, and arthritis patients might be able to live a more comfortable life.

According to the data already compiled by Wiley and his colleagues, the destruction of the substance P neurons does not inhibit normal pain signals, such as those which cause us to pull away from a hot stove before we are burned or stop from cutting ourselves when we feel something sharp.

"Those are examples of pain which has a protective function and are necessary parts of our makeup," said Wiley.

Further study in animal models may enable researchers to conduct small-scale studies in humans in about a year, said Wiley.