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June 16, 2022

University of Oxford team discovers gene linked to chronic pain

The latest findings showed that any drugs that can boost NCX3 activity could potentially decrease pain sensitisation in humans.

Researchers at the University of Oxford in the UK have identified a gene that regulates pain sensitisation by augmenting pain signals within the spinal cord.

This offers an insight into the key mechanism underlying chronic pain in humans and provides a new therapeutic target.

The team from the Nuffield Department of Clinical Neurosciences of Oxford initially compared genetic variation in samples obtained from more than 1,000 subjects from Colombia in a two-part study to see if there were any genetic variants more common in individuals with higher pain wind-up. 

Researchers found a substantial difference in variants of one specific gene, the protein Sodium Calcium exchanger type-3, NCX3.

Repeated stimulation such as with a sharp pin prick can cause increased sensitivity to pain, a process known as pain wind-up.

The team subsequently carried out a series of experiments in mice, to analyse the way NCX3 regulates pain wind-up and if it could become a treatment target. 

NCX3 was found in the mouse spinal cord neurons that process and send pain signals to the brain. 

These neurons required NCX3 to transfer the extra calcium that accumulates after activity. 

The spinal cord neurons were found to have increased activity in response to injury signals from the periphery and enhanced pain wind-up in NCX3’s absence.

On the other hand, enhancing the NCX3 levels within the spinal cord could reduce pain in the mouse.

The latest findings showed that any drugs that can boost NCX3 activity could potentially lower pain sensitisation in humans.

Nuffield Department of Clinical Neuroscience Neurology and Neurobiology professor David Bennett 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.”

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