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University of Cambridge scientists discover why some women don’t need pain relief during childbirth

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A study of women who did not need pain relief during childbirth has suggested that they may be carriers of a genetic variant that acts like a natural epidural.

Researchers discovered that it limits the ability of nerve cells to send pain signals to the brain.

About one in 100 women have a genetic variant that means they don't need pain relief during childbirth (38858990)
About one in 100 women have a genetic variant that means they don't need pain relief during childbirth (38858990)

It means that the pain threshold for the one in 100 women thought to carry this variant of the gene KCNG4 is much higher than normal.

The study was a collaboration between clinicians and scientists at Addenbrooke’s Hospital and the University of Cambridge.

Dr Michael Lee, from the university’s Division of Anaesthesia, recruited women who had carried their first-born to full term and did not request any pain relief during an uncomplicated vaginal delivery.

With colleagues, Dr Lee carried out tests including applying heat and pressure to their arms and getting them to plunge their hands into icy water.

They found they had higher pain thresholds than a control group of women who had experienced similar births but were given pain relief. They found no differences in emotional or cognitive abilities in either group.

Dr Lee, joint first author of the paper published in the journal Cell Reports, 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.”

Senior co-author Professor Geoff Woods and colleagues at the Cambridge Institute for Medical Research then sequenced the genetic code of both groups of women, discovering a higher-than-expected prevalence of KCNG4 variant among those in the test group.

KCNG4 codes for the production of a protein that forms part of a ‘gate’ that controls the electric signal flowing along our nerve cells.

Joint first author Dr Van Lu showed sensitivity of this gatekeeper to signals that could open the gate and turn nerves on was reduced by the variant.

Dr Ewan St John Smith, from the Department of Pharmacology, confirmed the finding in studies with mice, showing the threshold that opens the ‘defective’ gate and turn the nerve cell on was higher.

Dr St John Smith, senior co-author, 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 study could aid our understanding of pain management.

Senior co-author Professor Frank Reimann said: “Not only have we identified a genetic variant in a new player underlying different pain sensitivities, but we hope this can open avenues to the development of new drugs to manage pain.”

Professor David Menon, senior co-author, added: “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.” The research was supported by Addenbrooke’s Charitable Trust, the National Institute for Health Research Cambridge Biomedical Research Centre, Wellcome Trust, Rosetrees Trust and the BBSRC.

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