Painkillers genes

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Posted by Chonas ( on March 01, 2000 at 09:00:49:

Genes and gender explain part of the difference in how people feel pain, and also why some get more relief from painkillers than others do, scientists said Sunday.

These insights are emerging from research that is probing pain at its most basic levels, genes and proteins, and from computerized imaging of the brain in action. These studies might yield highly specific new pain drugs with few side effects, scientists said.

In the meantime, they said, the research is revealing some of the reasons why methods such as hypnosis and distraction can be effective pain-reducers.

When scientists at McGill University in Montreal monitored volunteers' brain activity using a functional MRI device, they saw that areas that are highly active when someone was focusing on a painful stimulus were significantly dampened when the person was distracted by a task, said Catherine Bushnell, a McGill psychologist.

"We saw pain signals decreased before they ever got to" a part of the brain where pain is perceived, Bushnell said. "You really can teach people to reduce their pain" through distraction or hypnotic suggestion, she said at the annual meeting of the American Association for the Advancement of Science.

Even so, some people apparently are genetically programmed to be more or less sensitive to pain, said other scientists, commenting on both animal and human research.

"Females are more sensitive to pain and respond less to analgesics," said Jeffrey Mogil, a psychologist at the University of Illinois in Champaign-Urbana. The differences are not large, he said, but have been demonstrated quite clearly in animals. The scientists said they could only guess at evolutionary reasons for this, but they said that because of these gender differences, females might need stronger doses of painkillers. It also has been found that even within gender, there are individual differences in feeling pain that are linked to still undiscovered genes.

These genes explain "why we don't all respond to pain in the same way, and why, for example, the same dose of morphine works better on some people than others," Mogil said.

He described breeds of mice, some of which are exquisitely sensitive to pain while others are stoic in the face of painful stimuli. In humans, he said, "whiners may actually be in more pain while macho types aren't."

In addition, said Mogil, it appears that males and females employ slightly different brain mechanisms in their response to pain. If true, he said, one implication might be developing gender-specific painkilling drugs.

The most daunting area of pain research, the scientists said, is in understanding and controlling chronic pain. While acute pain is a symptom that goes away when the cause is resolved, chronic pain is really a disease unto itself, said Allan Basbaum, chairman of anatomy at the University of California in San Francisco. "Persistent pain produces changes in the nervous system" so that the sensation continues long after it has been useful to the person.

Basbaum said that research has shown that, in cases of people who suffer from chronic pain, the brain makes proteins that it normally does not manufacture. That suggests that these proteins could be new targets for drugs that could selectively obliterate chronic pain without causing side effects. These findings have drawn molecular scientists to the field of chronic pain research.

If specific genes are misbehaving in some kinds of chronic pain, then gene therapy is a potential route of treatment, the scientists said. One strategy would be to replace or counteract the effect of the genetic pain culprit, they said. Another might be to give patients genes that cause brain and nerve cells to make larger amounts of endorphins, a natural painkiller in the body.

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