An extensive meta-analysis of data from the UK biobank has found a different genetic basis for chronic pain in women than in men.
The results are still preliminary, but to date this is one of the largest genetic studies of chronic pain to analyze the female and male sex separately.
“Our study emphasizes the importance of considering sex as a biological variable and showed subtle but interesting sex differences in the genetics of chronic pain,” said population geneticist Keira Johnston of the University of Glasgow in Scotland.
Chronic pain conditions are among the most common, debilitating, and expensive in public health. In the United States, chronic pain affects more people than heart disease, diabetes and cancer combined, and yet it receives a fraction of the total funding.
Even when studies are done, they often overlook the underlying gender differences, which is a huge and damaging overview. 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 conducted on male mice or male humans. This means that we know very little about how and why women suffer more and what treatments can best help them.
While there are likely multiple biological and psychosocial processes in this gender difference, the current genome-wide study suggests there is a genetic factor in the mix as well.
By comparing gene variants associated with chronic pain in 209,093 women and 178,556 men from the UK Biobank, researchers have tried to find at least some of the answer in our biology.
Ultimately, researchers found 31 genes associated with chronic pain in women and 37 genes associated with chronic pain in men with hardly any overlap. The authors admit that some of the differences here may be due to their lower male sample size, but the results are intriguing nonetheless.
When researchers tested the expression of all these genetic variants in different tissues from mice and humans, they found that the vast majority were active in a cluster of nerves in the spinal cord, known as the dorsal root ganglion, that send messages from the body to the brain.
Several genes in the male-only or female-only list were associated with psychiatric problems or immune function, but only one gene, known as DCC, was in both lists.
DCC encodes a receptor that binds with a protein crucial for the development of the nervous system, especially the dopaminergic system; The latter is not only a center of reward, but has recently been associated with pain modulation in the body.
DCC is also considered a risk gene for the pathology of depression, and DCC mutations occur in people with congenital mirror movement disorder, replicating movements on one side of the body on the other.
Exactly how DCC relates to chronic pain remains unclear, but the authors say their results support several theories “of a strong nervous system and immune involvement in chronic pain in both sexes,” which they hope will be used to provide better treatments in the future. to develop.
For example, if chronic pain is more strongly associated with immune function in women, the side effects of immune-targeted drugs can be very different than in men. On the other hand, treatments such as chronic opioid use can also have different results. Opioids are known to adversely affect immune function, suggesting that they may make things worse and not better for women with chronic pain.
At least these are just ideas at the moment. A lot more pain research needs to be done and a lot more done on women before we can really begin to understand the real gender differences at play and what we can do about it.
Taken together, these lines of evidence suggest putative central and peripheral neuronal roles for some of these genes, many of which have not been historically well studied in the field of chronic pain, the authors conclude.
The study is published in PLOS Genetics