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Toronto

THE discovery of a protein that determines how much pain we feel could lead
to more effective, non-addictive painkillers with fewer side effects than drugs
such as morphine.

A team at the University of Toronto has found that mice genetically modified
to lack a protein called DREAM are far less sensitive to all kinds of pain,
including the sharp, long-term pain caused by nerve injuries. 鈥淭his is exciting
because the medical community doesn鈥檛 currently have any widely effective
treatments for this type of pain,鈥� says team member Michael Salter.

DREAM stands for 鈥渄ownstream regulatory element antagonistic modulator鈥�. The
protein blocks the production of dynorphin, one of the body鈥檚 own painkillers,
or endorphins. So if you knock out DREAM, you increase levels of this natural
painkiller. This is a different mechanism to most painkillers, such as morphine,
which work by binding to the same receptors as endorphins. And unlike morphine,
such drugs should be non-addictive: when the researchers blocked the receptors
for dynorphin with another drug, the mice showed no withdrawal symptoms. They
behaved normally in other ways too, showing no problems with coordination,
learning or memory.

Salter says researchers will now be looking for ways to target DREAM in
people. One strategy would be to find small molecules that would bind to DREAM
and stop it working. Another is to use antisense technology鈥攃omplementary
molecules that bind to the single-stranded messenger RNAs that code for DREAM
and prevent them being read by a cell鈥檚 protein-making factories.