Women often suffer from pain longer than men. A study now provides a biological explanation: According to this, the reduction of pain is actively controlled by certain immune cells, the so-called monocytes. These release the messenger substance interleukin-10 (IL-10) and in this way dampen the pain fibers. However, the IL-10 level in men is significantly higher than in women and their cells have more receptors for the anti-pain signal. Experiments on mice show that the male sex hormone testosterone plays an important role in this. The findings could help develop novel therapies for acute and chronic pain.
When we injure ourselves, our pain-conducting nerve fibers sound the alarm: They send signals to our brain that ensure that we feel pain and then quickly move the affected part of the body out of the danger zone and protect it during the healing phase. The same mechanism also occurs with inflammation and also serves to protect our body. But the pain doesn’t always stop when the inflammation has subsided or the wound has healed. In many people, the pain sensors remain permanently active or become oversensitive and cause chronic pain. Women are affected by this much more often than men.
Active process of the immune system
A team led by Jaewon Sim from Michigan State University has now found a possible explanation for these gender differences in experiments on mice. For their experiments, the researchers first caused pain in male and female mice by either cutting their legs with a blade or injecting them with a substance that causes severe, painful inflammation. In the days following the procedure, the test animals of both sexes flinched when the injured or inflamed leg was lightly touched – an indication of significant pain. But after about a week, the males slowly became less sensitive, while the pain response in the females continued.
Further analyzes showed that the males had significantly higher levels of the messenger substance interleukin-10 (IL-10), which is secreted by a group of white blood cells called monocytes, in the affected tissue. IL-10 not only has an anti-inflammatory effect, but also binds directly to nerve fibers and signals to them that it is time to turn off the pain. If the researchers blocked the IL-10 receptors, the male test animals also suffered from pain for longer. “This study shows that the resolution of pain is not a passive process,” said Sim’s colleague Geoffroy Laumet. “It’s an active, immunological process.”
Controlled by testosterone
But why do monocytes produce more IL-10 in males than in females? What influence do sex hormones have? To answer this question, the researchers removed the ovaries of some female mice and injected them with the male sex hormone testosterone. And indeed: In these animals, the monocytes released more IL-10 and their pain subsided more quickly. On the other hand, if the researchers blocked the testosterone receptors of their monocytes in male mice, the IL-10 level remained low and the pain persisted.
Sim and his team also analyzed data from 245 people who suffered from pain after accidents. They also showed the same pattern: men’s IL-10 levels were higher and their pain decreased more quickly. While those affected of both genders rated their pain intensity similarly immediately after their accident, the men reported significantly less pain three months later. “The difference between pain in men and women has a biological basis,” says Laumet. “Women don’t just imagine the pain and they’re not complaining. It’s because of their immune system.”
The results could also help to find new approaches to pain therapy in the long term. When the researchers gave the injured mice a substance called resolvin D1, which promotes the production of IL-10-releasing monocytes, the pain subsided more quickly in both sexes. “This opens up new avenues for non-opioid therapies aimed at preventing chronic pain before it becomes established,” says Laumet.
Source: Jaewon Sim (Michigan State University, East Lansing, USA) et al., Science Immunology, doi: 10.1126/sciimmunol.adx0292