AFP - Thursday, January
17
Conquering
chronic pain: scientists find a key
PARIS (AFP) - - 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 Organisation (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 organisations.