In a study published this week in the journal Cell Reports, researchers from the University of Cambridge and Addenbrooke’s Hospital, have found that women who do not need pain relief during childbirth may be carriers of a key genetic variant that acts a natural epidural.
Childbirth is widely recognised as a painful experience. However, every woman’s experience of labour and birth is unique, and their level of discomfort and pain during labour varies substantially.
Professor Frank Reimann and Dr Van Lu (Reimann-Gribble group) were part of the collaborative team who studied a group of women who had carried their first-born to full term and did not request any pain relief during an uncomplicated delivery compared to a control group who had. Tests carried out by the researchers included applying heat and pressure to the women’s arms and getting them to plunge their hands into icy water, the results of which demonstrated higher pain thresholds in the test group.
After sequencing the genetic code of both groups of women they discovered that those in the test group had a higher-than-expected prevalence of a rare variant of the gene KCNG4 (an estimated 1 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. Similar proteins are found in electrically active cells that regulate metabolism such as pancreatic beta cells and enteroendocrine cells, which the Reimann-Gribble group studies. As the joint first author Van Lu showed the 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 by Dr Ewan St. John Smith from the Department of Pharmacology, who showed that the ‘defect’ in the formation of the switch on the nerve cells was in fact, acting like a natural epidural resulting in much stronger contractions during labour being required to switch it on.
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 Frank Reimann (Senior co-author)
The research was support by the Addenbrooke’s Charitable Trust, the National Institute for Health Research Cambridge Biomedical Research Centre, Wellcome, Rosetrees Trust and the BBSRC.