Medicine: The Painkillers

Medicine's most powerful weapons against pain are the opiates, substances such as heroin and morphine that are derived from opium. But only in the past few years have scientists understood why and how the human body responds to these drugs from the poppy plant. For contributing to that understanding, three men last week won the Albert and Mary Lasker Foundation's prestigious Basic Medical Research Award.

Sharing the $15,000 prize were Dr. Hans Kosterlitz of the University of Aberdeen in Scotland, Pharmacologist John Hughes of the Imperial College of Science and Technology in London and Dr. Solomon Snyder of Baltimore's Johns Hopkins University.

Snyder and his co-workers discovered in 1973 that the nerves of the brain and spinal cord contain specific sites to which opiates must bind in order to produce their effect. Morphine and similar drugs fit into these so-called opiate receptors like a key into a lock. Once in the lock, the drugs are able to dampen pain signals to the brain. Snyder then went on to map the distribution of the receptors in the brain. Kosterlitz and Hughes expanded on the research. They wondered why the body should evolve receptors for foreign narcotics; perhaps the body produced its own opiates. In 1975 they discovered and isolated two such compounds from pig brains and dubbed them enkephalins (from the Greek words for in the head).

Enkephalins seem to be present in all vertebrates. They are part of the body's protective biochemical system for coping with pain and stress. Scientists suggest that people who can stand more pain than others may be able to call forth extra supplies of enkephalins. Those with a low tolerance for pain may be deficient in either receptor sites or enkephalins.

The discoveries also help explain narcotic addiction. Scientists speculate that under normal conditions, enkephalins bind to a certain number of receptor sites. Morphine acts to relieve pain by filling the remaining sites. But too much morphine overloads the system, causing enkephalin production to be cut off. More morphine is needed to fill the receptors and produce relief. If the narcotic is then withheld, all the receptors remain empty, resulting in typical withdrawal symptoms. With this knowledge, researchers hope to design nonaddictive pain relievers.

The enkephalins appear also to affect emotions. In mapping receptor sites Snyder found that the amygdala, a small portion of the brain that has no known role in physical pain but plays a major part in regulating the emotions, is unusually rich in opiate receptors. Thus variations in the number of receptors, or in the concentration of enkephalins—or the presence of narcotics—at these sites may affect emotions and behavior. Said Kosterlitz at the Manhattan award presentation: "The discovery of the enkephalins resembled the opening of Pandora's box, hopefully this time for the benefit of mankind."