Drug that can wipe away pain memories

05 December 2010


Scientists have discovered that they can switch off chronic pain by wiping out the brain's memory for the event that caused the discomfort. Chronic pain is a significant health problem for sufferers and also places a considerable economic and treatment burden on healthcare providers. But now, in a paper published this week in the journal Science, researchers have shown that certain kinds of pain sensation are very much "in the mind" and can be erased with a drug.

Image of Golgi stained neurons in the dentate gyrus of an epilepsy patient. 40 times magnification.University of Toronto scientist Xiang-Yao Li made the discovery by working with mice genetically engineered to express a glowing green gene in neurones that had been affected by nerve injuries.  When the common peroneal nerve, which supplies the hind limb was ligated in a group of mice, cells in the front part of the brain called the anterior cingulate cortex, lit up green.  At the same time these animals showed signs of developing allodynia - or neuropathic pain - a condition of enhanced sensation in which normally innocuous stimuli - such as light brushing of a patch of affected skin - are experienced as extremely painful.

But when the team injected a chemical called ZIP (which stands for zeta-pseudosubstrate inhibitory peptide) into the anterior cingulate cortex, the allodynia symptoms vanished. ZIP inhibits an enzyme called phosphokinase M zeta (PKM-zeta).

This appears to play a critical role in controlling the strength of the synaptic connections between nerve cells.  So when something is learned, PKM-zeta increases its activity in the synapse and sensitises the target nerve cells to nerve transmitter chemicals.  PKM-zeta also promotes its own activity, helping to sustain nerve connections in their learned state.

But if ZIP is injected, this inhibits the enzyme, weakening the nerve connection and also preventing further PKM-zeta activity.  Effectively it wipes away learning, and when injected into the anterior cingulate cortex the fact that it was able to make symptoms of allodynia disappear in awake animals indicates that some chronic pain states are "learned" by the brain and that it might be possible to use approaches like this to wipe the neurological slate clean and reset pain thresholds in patients.


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