A comprehensive meta-analysis of data from the UK Biobank found a different genetic basis for chronic pain in women compared to men.
The results are still preliminary, but to date, this is one of the largest genetic studies on chronic pain to analyze female and male separately.
“Our study highlights the importance of considering sex as a biological variable and showed subtle but interesting sexual differences in chronic pain genetics,” says population geneticist Keira Johnston of the University of Glasgow in Scotland.
Chronic pain conditions are among the most common, disabling and most expensive public health conditions. In the United States, chronic pain affects more people than heart disease, diabetes and cancer combined, and yet it receives a fraction of global funding.
Even when studying, they often overlook the underlying sexual differences, and this is a huge and harmful surveillance. Compared to men, women are much more likely to develop multiple chronic pain disorders, and yet, historically, 80 percent of all pain studies have been performed on male mice or males. . This means that we know very little about how and why women suffer the most and what treatments can best help them.
While there are probably several biological and psychosocial processes in this sexual discrepancy, the current study of the entire genome suggests that there is also a genetic factor involved.
Comparing the genetic variants associated with chronic pain in 209,093 women and 178,556 men in the UK Biobank, the researchers tried to find at least some of the answer in our biology.
Finally, the researchers found 31 genes associated with chronic pain in women and 37 genes associated with chronic pain in men with barely overlapping. The authors acknowledge that some of the differences here may be due to their smaller size of the male sample, but the results are still interesting.
When the researchers tested the expression of all these genetic variants in different tissues from mice and humans, they noticed that the vast majority were active in a group of nerves in the spinal cord, known as the dorsal root ganglion, which sends messages from the body to the brain. .
Several genes on the men’s or women’s-only list were associated with psychiatric problems or immune function, but only one gene, known as DCC, was on both lists.
DCC encodes a receptor that binds to a protein crucial for the development of the nervous system, especially the dopaminergic system; In addition to being a reward center, the latter has recently been connected to the modulation of pain in the body.
DCC is also considered to be a risk gene for the pathology of depression, and DCC mutations occur in those with congenital mirror movement disorder, which leads to movements on one side of the body that are reproduced on the other side.
How exactly DCC is related to chronic pain remains unclear, but the authors say their findings support several theories of “strong nervous system and immune involvement in chronic pain in both sexes,” which they hope will be used to develop treatments. better in the future.
If chronic pain is more strongly associated with immune function in women, for example, the side effects of drugs aimed at immunity may be very different from men. On the other hand, treatments such as chronic opioid use may also have different results. Opioids are known to adversely affect immune function, suggesting that they could make things worse and not better for women with chronic pain.
For now at least, these are just ideas. Much more pain research is needed and much more needs to be done before we can really begin to understand the real sexual discrepancies at play and what we can do about it.
“All these lines of evidence, together, suggest putative central and peripheral neural roles for some of these genes, many of which have not been well studied historically in the field of chronic pain,” the authors conclude.
The study was published in PLOS Genetics.