Genetic variant in some women acts as a natural epidural

Thursday, 30 July, 2020

Genetic variant in some women acts as a natural epidural

Women who do not need pain relief during childbirth may be carriers of a key genetic variant that acts as a natural epidural.

That’s according to scientists from the University of Cambridge, whose study in the journal Cell Reports explains how the variant limits the ability of nerve cells to send pain signals to the brain.

Every woman’s experience of labour and childbirth is unique, and the level of discomfort and pain experienced during labour varies substantially between women. A collaboration between clinicians and scientists based at Addenbrooke’s Hospital, part of Cambridge University Hospitals NHS Foundation Trust (CUH), and the University of Cambridge sought to investigate why some mothers report less pain during labour.

The researchers recruited a group of women, all of whom had carried their first-born to full term and did not request any pain relief during an uncomplicated vaginal delivery. A number of tests were carried out on the women, including applying heat and pressure to their arms and getting them to plunge their hands into icy water.

Compared to a control group of women that experienced similar births but were given pain relief, the test group showed higher pain thresholds for heat, cold and mechanical pressure, consistent with them not requesting pain relief during childbirth. The researchers found no differences in the emotional and cognitive abilities of either group, suggesting an intrinsic difference in their ability to detect pain.

“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,” said Dr Michael Lee, joint first author on the study. “When we tested these women, it was clear their pain threshold was generally much higher than it was for other women.”

Next, researchers at the Cambridge Institute for Medical Research sequenced the genetic code of both groups of women and found that those in the test group had a higher-than-expected prevalence of a rare variant of the gene KCNG4. It’s estimated that approximately one in 100 women carry this variant.

KCNG4 provides the code for the production of a protein that forms part of a ‘gate’, controlling the electric signal that flows along our nerve cells. As joint first author Dr Van Lu showed, sensitivity of this gatekeeper to electric signals that had the ability to open the gate and turn nerves on was reduced by the rare variant. This was confirmed in a study involving mice, which showed that the threshold at which the ‘defective’ gates open, and hence the nerve cell switches ‘on’, is higher — which may explain why women with this rare gene variant experience less pain during childbirth.

“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,” said Dr Ewan St. John Smith, senior co-author on the study. “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.”

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

Image credit: © Bilkei

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This is a modified version of a news item published by the University of Cambridge under CC BY 4.0.

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