The team, funded by the Biotechnology and Biological Sciences Research Council and working at University College London (UCL), have shown for the first time that genes involved in chronic pain are regulated by small RNAs. This mechanism is so different from what has already been discovered about the biology underpinning pain that it could be the Achilles heel of chronic inflammatory pain, which is notoriously difficult to treat.

Lead researcher Professor John Wood from UCL commented: ‘When a person experiences chronic pain as a result of some sort of inflammation – as in arthritis – their pain threshold goes down very dramatically. What they can normally do without pain, such as walking or putting on clothes, becomes very painful.

‘Chronic inflammatory pain can be treated with pain-killing drugs – analgesics – but these usually have an impact on the whole body and may also dull our experience of acute pain, which is actually very important as it protects us from injury.

‘What we would really like to be able to do is return the pain thresholds to normal in a person who has chronic inflammatory pain, rather than just numbing the whole body. This would mean that they still get the protection of acute pain. Currently, aspirin-like drugs that can do this have a number of side-effects but the present discovery might make it possible to invent a class of drugs that act in a completely novel way.’

The researchers studied mice that lack the enzyme Dicer and found they respond normally to acute pain but are unaffected by stimuli that usually cause chronic inflammatory pain. This is because Dicer makes small RNAs, which – as we now know – are required for the regulation of genes involved in chronic inflammatory pain.

Without Dicer, the small RNAs aren’t made, and without the small RNAs, many of these genes are expressed at low levels. So, for example, molecules such as sodium channels that make pain nerves responsive to inflammation are produced at low levels and, therefore, inflammatory pain is not detected by the mouse’s body.

Professor Wood concluded, ‘Knowing that small RNAs are so important in chronic inflammatory pain provides a new avenue for developing drugs for some of the most debilitating and life-long conditions out there.’

Further reading

Zhao et al. (2010) Small RNAs control sodium channel expression, nociceptor excitability, and pain thresholds. J. Neurosci. 30 10860–10871