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Rare genetic variant ‘acts as natural epidural’ during childbirth

Around one in 100 women are thought to carry the variant of the KCNG4 gene.
Around one in 100 women are thought to carry the variant of the KCNG4 gene. Around one in 100 women are thought to carry the variant of the KCNG4 gene.

A rare genetic variant may explain why some women do not require pain relief during childbirth, scientists have said.

Researchers from the University of Cambridge say they have found a rare variant of the gene KCNG4 to be associated with a lower pain threshold, acting “like a natural epidural”.

The researchers say their findings, published in the journal Cell, could “open avenues to the development of new drugs to manage pain”.

Around one in 100 women are thought carry this genetic variant, which scientists believe plays a role in reducing the ability of nerve cells to send pain signals to the brain.

Dr Ewan St John Smith from the university’s department of pharmacology, and senior co-author on the study, said: “The genetic variant that we found in women who feel less pain during childbirth leads to a ‘defect’ in the formation of the switch on the nerve cells.

“In fact, this defect acts like a natural epidural.

“It means it takes a much greater signal – in other words, stronger contractions during labour – to switch it on.

“This makes it less likely that pain signals can reach the brain.”

The researchers studied a group of women who gave birth to their first child during an uncomplicated vaginal delivery and did not request pain relief.

Tests showed that compared to a control group, this group of women showed higher tolerance for heat, cold and mechanical pressure.

Dr Michael Lee, from the university’s division of anaesthesia and joint first author on the study, said: “It is unusual for women to not request gas and air, or epidural for pain relief during labour, particularly when delivering for the first time.

“When we tested these women, it was clear their pain threshold was generally much higher than it was for other women.”

The team sequenced the genetic code of both groups of women and found that those in the test group had the rare KCNG4 gene variant.

KCNG4 helps facilitate the production of a protein that acts like a “gate”, controlling the electric signal that flows along through nerve cells to the brain.

The sensitivity of this so-called gatekeeper to electric signals that had the ability to open the gate and turn nerves on was reduced by the rare variant, the researchers said.

Professor David Menon, senior co-author on the study, said: “This approach of studying individuals who show unexpected extremes of pain experience also may find wider application in other contexts, helping us understand how we experience pain and develop new drugs to treat it.”