Gene involved in chronic pain
Thursday June 16th 2022
A gene has been discovered that regulates pain sensitisation by amplifying pain signals within the spinal cord.
Writing in *Neuron*, researchers at Oxford University, UK, say their findings can help them to understand an important mechanism that underlies chronic pain and could lead to a new treatment target.
In a two-part study, researchers from Oxford’s Nuffield Department of Clinical Neurosciences compared genetic variation in samples from more than 1,000 participants from Colombia, to see if there were any genetic variants that were more common in people who experienced greater pain wind-up.
When they discovered a significant difference in variants of one specific gene, the protein Sodium Calcium exchanger type-3 (NCX3), they carried out experiments in mice to understand how NCX3 regulates pain wind-up and to see if could be a treatment target.
They found NCX3 was expressed in the mouse spinal cord neurons that process and transmit pain signals to the brain.
These neurons needed NCX3 to export the excess calcium that builds up following activity, but if there was no NCX3 the spinal cord neurons showed more activity in response to injury signals from the periphery and pain wind-up was increased.
Increasing NCX3 levels within the spinal cord were also found to reduce pain in the mouse.
Professor David Bennett, professor of Neurology and Neurobiology of the Nuffield Department of Clinical Neuroscience, said: “This is the first time that we have been able to study pain in humans and then to directly demonstrate the mechanism behind it in mice, which provides us with a really broad understanding of the factors involved and how we can begin developing new treatments for it.
“The findings imply that any drugs which can increase activity of NCX3 would be predicted to reduce pain sensitisation in humans.”
Trendafilova T, Adhikari K, Schmid AB et al. Sodium-calcium exchanger-3 regulates pain ‘wind-up’: from human psychophysics to spinal mechanisms. *Neuron* 14 June 2022.
Tags: Genetics | Pain Relief | UK News
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