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Nature publication on pain research
Date:1/22/2008

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GABAA receptors as pain targets

It had been acknowledged for some time that GABA serves important functions in pain control. That benzodiazepines act on at least four different subtypes of GABA receptors was also known. Nonetheless, these receptors were largely neglected as potential targets for pain treatment.

The research team led by Ulrich Zeilhofer used genetically altered mice in experiments to target the GABA receptors that control spinal pain relay. They first induced a slight inflammation in one hind paw or irritated the sciatic nerve to induce pain. A few days later the mice received an injection of a benzodiazepine close to the spinal cord. Experiments with the mice allowed the researchers to identify two subtypes of GABAA receptors which mediate spinal pain control.

A challenge for drug design

For experiments with animals, drugs with the proposed receptor specificity are already available. Such experiments have confirmed that the pharmacological enhancement of spinal GABA receptor function inhibits the relay of pain signals to the brain. Further studies have also shown that these compounds did not lose their analgesic effects during prolonged treatment and did not lead to addiction.

Successful design of a drug that targets only those two subtypes of GABA receptors would be a big step forward in pain therapy. Chronic pain could be treated specifically and with fewer side effects. The challenge is now for pharmaceutical companies to develop drugs that specifically target these receptors in humans, says Zeilhofer.


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Contact: Professor Hanns Ulrich Zeilhofer
hansze@ethz.ch
41-044-635-5912
ETH Zurich/Swiss Federal Institute of Technology
Source:Eurekalert

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