A meta-analysis of UK genetic data has found a different genetic basis for chronic pain in women compared to men.
While the results are still preliminary, this is one of the largest genetic studies on chronic pain analysing by sexes.
“Our study highlights 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 prevalent, disabling, and expensive conditions in public health, and are frequently overlooked for research funding. With 100 million people in chronic pain in the US in 2016, overprescription of opioids for chronic pain has resulted in an epidemic of opioid misuse, with 66% of overdose cases being for opioids. Even very moderate opioid use carries the risk of addiction and abuse.
Even when studies are done, they often overlook underlying sex differences, and that’s a huge and detrimental oversight. Compared to men, women are far 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 we know very little about how and why females are suffering more and what treatments can help them best.
While there are probably multiple biological and psychosocial processes in this sex discrepancy, the current genome-wide study suggests there’s a genetic factor in the mix, too.
The researchers compared gene variants associated with chronic pain in 209 093 women and 178 556 men from the UK Biobank, and found 31 genes associated with chronic pain in women and 37 genes associated with chronic pain in men with barely any overlap. This might be due to the slightly smaller sample size of men but the results are nonetheless intriguing, the researchers maintained.
The vast majority of these genes were active in a cluster of nerves within the spinal cord, known as the dorsal root ganglion, which transmits messages from the body to the brain.
While several genes in the male-only or female-only list were linked with psychiatric disorders or immune function, only one, called DCC, was found in both lists.
DCC encodes for a receptor that binds with a protein crucial for the development of the nervous system, especially the dopaminergic system. The dopaminergic system is the ‘reward centre’ but also has been linked to pain.
DCC is also linked to depression, and DCC mutations appear in those with congenital mirror movement disorder, which results in movements on one side of the body being replicated on the other side.
It’s not how DCC is linked to chronic pain, but the researchers believe their results support several theories “of strong nervous system and immune involvement in chronic pain in both sexes”, which will, they hope, result in the development of better treatments.
Should chronic pain be more closely linked to immune function in women, immune-targeting drugs may have very different side-effects than in men. Opioids negatively impact immune function, indicating that they could in fact worsen the situation for women suffering chronic pain. However, more research is needed to strengthen these findings and understand their impacts.
“All of these lines of evidence, together, 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 concluded.
Source: Science Alert
Journal information: Johnston KJA, Ward J, Ray PR, Adams MJ, McIntosh AM, Smith BH, et al. (2021) Sex-stratified genome-wide association study of multisite chronic pain in UK Biobank. PLoS Genet 17(3): e1009428. doi.org/10.1371/journal.pgen.1009428
