Experimental drugs may aid treatment in chronic pain cases HURTING FOR RELIEF

January 24, 1995|By Jamie Talan | Jamie Talan,Newsday

Take an aspirin and call back in, well, a few years. That's how long it may take for the next generation of painkillers to arrive.

But they are coming, and researchers say these new and powerful substances -- born from the most advanced knowledge of how pain messages travel from the periphery to the brain -- will revolutionize pain treatment for chronic conditions such as migraines and arthritis.

"It is a very exciting time," said Allan L. Basbaum, professor of anatomy and physiology at the Keck Center for Integrative Neuroscience at the University of California, San Francisco. "Some of these substances are remarkable."

At last fall's meetings of the Society for Neuroscience and American Pain Society, scientists were eagerly sharing snippets of work -- from how a key pain transmitter called Substance P works in the body to the chemical underpinnings of the pain response.

As researchers continue to unravel the mysteries of the ouch, pharmaceutical companies are taking these findings and developing the next generation of substances to quell a variety of aches and pains.

Some of the new research includes:

* Experimental drugs that block substance P, a neurochemical crucial to the complex pain process;

* A substance derived from marine cone snails that reduces pain without causing numbness;

* PET scan studies of pain in action;

* Adrenal cell transplants that bathe nerve cells in pain-relieving natural substances called opioids and catecholamines.

Millions of people suffer from chronic pain conditions and spend billions on medicines that offer marginal relief. The old standards of pain relief -- morphine and aspirin and their chemical cousins -- work well on acute forms of pain, but offer little comfort for those with long-lasting and severe pain conditions.

What is pain, anyway?

According to Dr. Basbaum, "Pain is a complicated perception that is influenced not only by the amount of sensory input, but also by mood and experience."

Some kinds of pain are straightforward responses to injury. When a cook burns herself, for instance, the heat triggers sensory neurons called nociceptors, which transmit the pain signal to the spinal cord. From there, the signal is sent to the brain.

In such cases, the input message at the nociceptor is key to the pain signal. But researchers are finding that in chronic pain this input message is less important, and more activity seems to be generated in the central nervous system itself.

For a minor injury, topical lotions such as lidocaine can be used to block nerve transmission at the site, so that information about the painful experience never reaches the central nervous system. Numbness occurs when all the pain information is shut off.

How such drugs as aspirin and morphine work is far more complex. Studies have shown that morphine, for instance, acts on at least three different places in the brain. It works on opiate receptors, of which there are at least seven different types, to make use of the naturally occurring processes that the body uses to block pain transmission.

The new compounds that scientists are developing target chronic pain, which doesn't really respond to current pain-altering medicines.

One extremely effective compound, according to federal researchers at the National Institute of Dental Research, is omega-conopeptide, one of several toxic substances that marine cone snails use to kill their prey. The researchers are testing an omega-conopeptide formulation called SNX-11, developed by the California biotech firm Neurex.

The substance is so promising, says Gary Bennett, chief of the s neuropathic pain division at the National Institute of Dental Research, that he feels "it's probably better than the most active drugs to date."

Unlike other potent pain medicines, omega-conopeptides do not cause numbness or paralysis around the injured area because they do not interfere with normal nerve conduction. Instead, these substances work by blocking the abnormal spontaneous nerve impulses that are characteristic of chronic pain, Dr. Bennett said.

"We are excited," he said. "Just a drop at the site of a chronic pain injury and the pain seems to go away."

So far, animal studies suggest only minor side effects of omega- conopeptides: a small release of histamines and a slight climb in blood pressure, the equivalent of walking up the stairs.

Researchers say chronic pain signals work in much the same way a memory is stored, eventually making cells hyper-excitable to a familiar sensation.

"Chronic pain changes the way the nervous system primes itself for future messages," said Jacqueline Sagen, a University of Chicago neurobiologist.

Chronic pain initiates a series of events in the nervous system that leads to its cumulative effects, Dr. Sagen's studies suggest. An injury -- or a chronic hypersensitivity -- causes peripheral nerves to release abnormally high levels of an excitatory neurotransmitter called glutamate.

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