Women with chronic pelvic pain prescribed gabapentin sitting on the couch holding stomach area.
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Women with chronic pelvic pain who also carry a genetic variant in the neuregulin 3 gene (NRG3) are more likely to respond to treatment with gabapentin, shows research led by the University of Edinburgh.

Up to 26% of women and those assigned female at birth have chronic pelvic pain. Although this is sometimes diagnosed as being a symptom of conditions such as endometriosis through investigative procedures such as laparoscopy, in around 55% cases the reason for the pain remains unknown.

Women with chronic pelvic pain are often prescribed gabapentin, an anticonvulsant and neuropathic pain-relieving drug. A trial testing its efficacy in women with this condition (published in 2020) showed no significant benefits versus placebo overall. However, a further analysis of the data showed that around 40% of the women given gabapentin did have some benefit from the treatment.

The current study, published in iScience, tested 71 women from the earlier study to assess why some responded to the drug and some did not.

A genomic analysis revealed that a specific genetic variant found in a non-coding region of NRG3 (rs4442490) significantly predicted gabapentin pain response (area under the receiver operating characteristic curve score of 0.82).

“A genetic factor that can predict how well gabapentin will work in patients offers the prospect of tailored treatment and provides invaluable insights into understanding chronic pain,” said first author Scott Mackenzie, a researcher at the University of Edinburgh’s Centre for Reproductive Health, in a press statement.

“We hope eventually to use this genetic marker to optimize personalized treatment decisions and minimize adverse effects for women with chronic pelvic pain.”

The researchers looked for information about the function of the rs4442490 variant in a large sample from the UK Biobank including both genetic and brain imaging data. They showed that there were differences in brain features in those with the variant, suggesting they may have a neurological difference that explains why gabapentin is more effective for them than the general population.

“Many groups have demonstrated that genetic variants in the NRG3 gene are implicated in a range of neurodevelopmental and psychiatric disorders, including developmental delay, cognitive impairment, attentional deficits, and psychotic disorders such as schizophrenia. Additionally, recent evidence shows common genetic variants link chronic pain phenotypes and many neuroimaging traits,” write the authors.

“Here we find support for the neurobiological impact of NRG3 in the context of gabapentin efficacy in treating chronic pelvic pain… Successful replication or validation would provide stronger evidence to support the biological involvement of NRG3 and pave the way for the potential utility of a SNP-based test to predict drug response and stratify individuals likely to benefit from gabapentin treatment.”

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