Scientists find key to conquering pain
January 18, 2008, 12:00 am TWN
PARIS -- Scientists have found a substance that, in mice, blocks chronic pain but does not appear to cause any of the unwanted side effects of existing painkillers, according to a study released on Wednesday.
Researchers led by Hanns Zeilhofer at the University of Zurich in Switzerland found the compound after exploring the way pain signals travel up to the brain via the spinal cord.
“Normally the spinal cord acts as a kind of filter, ensuring that not all painful signals coming from the periphery of the body reach the brain,” Zeilhofer told AFP in an interview.
If these neurological gatekeepers were totally absent, even the lightest touch on the skin would make us wince with discomfort, he explained. “We would be in constant pain without them.”
But in patients with chronic pain, this filter function is impaired, meaning that the spinal cord is like an open channel for pain signals, he said.
A key role in the inhibition process is played by two nervous-system chemicals, called neurotransmitters.
One is gamma-aminobutyric acid, also known as GABA, and the other is glycin.
“We thought we could restore the filter function if we pharmacologically enhance the action of GABA or glycin in the spinal cord,” said Zeilhofer.
But as no compounds had been developed that target glycin, they focused instead on GABA.
In experiments reported in the British journal Nature, the researchers induced inflammation in the paws of mice and rats, and then gauged the force needed to make the animal withdraw its leg, creating a rough measure of pain.
First they injected Valium into the spinal cord. As predicted, the drug increased the transmission of GABA, significantly reducing the rodents’ aversive reactions.
But the problem with Valium as a treatment for pain is that it also causes drowsiness, impairs memory formation and rapidly loses its effectiveness, said Zeilhofer.
All these unwanted side-effects occur in the brain, he noted, so he and his team wondered if there wasn’t another chemical that would act only on the spinal cord.
That’s when they found L-838,417, a compound that suppressed the pain signals without causing sedation or losing its effectiveness over time.
“During a nine-day treatment in rats, we found the morphine completely lost its analgesic effect, whereas the analgesic effect of L-838,417 was completely retained,” Zeilhofer said.
Although the drug blunted chronic pain, it did not cause numbness that blocks acute pain — the sharp sensation that comes from burning or a cut, for instance. Acute pain is a vital survival mechanism.
Zeilhofer hopes that pharmaceutical companies will refine L-839,417 so that it can be approved for trials on humans.
“We are very keen to test such compounds in human pain models, first healthy volunteers and then in certain pain patients,” he said.
Worldwide, one in five people suffer from moderate to severe chronic pain caused by rheumatoid arthritis, nerve damage caused by injuries, diabetes and other diseases, according to the World Health Organization (WHO) and the International Association for the Study of Pain.
Among chronic pain sufferers, a third cannot maintain an independent lifestyle and as many as two-thirds sleep poorly, are unable to drive a car or have difficulties having sex.
Some 50 percent of adults who die in hospitals experience moderate to severe pain in the period immediately before death, according to these organizations.