Pain is something most people experience after an injury, whether from a sprained ankle, surgery or car accident. Normally, pain fades as the body heals. But it may last longer in women than in men, making women more likely to develop chronic pain.
For decades, differences in pain between men and women have often been attributed to psychological, emotional or social factors. Because of that, persistent pain in women is often overlooked in care.
However, my research team’s newly published study suggests that the immune system may play a role in why recovery from pain differs in men and women. Doctors have thought that the immune system increases pain by causing inflammation, which is often experienced as redness and swelling.
But recent work from my lab and others suggests that immune cells may also be critical to helping pain resolve, and differences in how these cells function between men and women may influence how quickly pain goes away.
Hormones and immune cells
I am a neuroimmunologist who studies how the nervous and immune systems communicate. My research team aims to understand why pain sometimes persists long after an injury has healed, eventually becoming chronic.
To study this process, we combined experiments in mice with data from people who had been involved in motor vehicle collisions. This type of injury is a common trigger for long-term musculoskeletal pain, making it an ideal situation to study how acute pain becomes chronic.
We focused on a specific molecule called interleukin-10 that helps reduce inflammation, measuring its levels in both mice after skin injury and in people in the emergency room after a motor vehicle accident. Surprisingly, we found that IL-10 doesn’t just calm inflammation. It also communicates directly to pain-sensing nerve cells to switch them off. In other words, IL-10 helps pain to go away.
We identified that IL-10 was mostly produced by a type of immune cell called monocytes that circulate in the blood and travel to injured tissues.
Across both mice and humans, we found that males tended to recover from pain more quickly than females. The reason appears to lie in how monocytes behave after injury. In males, these immune cells were more likely to produce IL-10, the molecule that helps resolve pain. In females, this response was less pronounced.
Importantly, we also found that testosterone influences how much IL-10 these immune cells produce. Higher levels of testosterone in males promoted higher production of IL-10 by monocytes.
This finding suggests that hormonal signals may shape the body’s ability to naturally turn off pain after injury.
Avenues for treatment
Our results point to a shift in how scientists think about pain: Rather than viewing the immune system only as a driver of pain, it may also be a key player in resolving it. Differences in immune cell function could explain why some people recover quicker from injury while others go on to develop chronic pain.
Understanding these biological pathways could eventually lead to new treatments. Instead of simply blocking pain signals, future therapies might aim to boost the body’s own pain resolution system. Helping immune cells calm down pain-sensing neurons more effectively could more quickly restore comfort after injury.
While more research is needed, these results highlight a promising new direction in the effort to prevent and treat chronic pain and better understand sex differences in pain.
