A growing body of research has shown that the human body can "remember" the pain of newborn injuries—including life-saving surgeries—all the way into adolescence. These early experiences appear to change how a child's pain response system develops at a genetic level, resulting in more intense reactions to pain later in life. Such changes also appear to occur more often among females.
Now, research led by experts at Cincinnati Children's has pinpointed how and where the genetic changes that create such long-lasting pain memory occur. According to their study, published in Cell Reports, the key changes are occurring in developing macrophage cells. The experiments show that an epigenetic change occurs in macrophages after an early-life injury, which in turn promotes more-intense pain responses to other injuries that occur later in life. Interestingly, male mice experiencing similar early-life injury showed the same epigenetic changes but did not sustain the same long-term pain memory as females.
Further testing also showed that changes, occurring in a gene called p75NTR, can be found in human macrophage cells. In female mice, the pain memory effects were detected for more than 100 days after the initial injury, which in humans would be roughly 10-15 years. This new understanding of neonatal pain memory underscores fundamental differences that exist between the genetic activity of a still-developing newborn immune system versus the mature system adults have.
The researchers suggest that simply changing pain medication doses may not be the answer, as there is a balancing act between controlling pain and minimizing the possible harmful side effects of existing medications. Instead, they believe there's a need to develop more-specific, better-targeted treatments that could prevent the re-programming of macrophage cells in response to injury. While blocking the p75NTR receptor in young mice did blunt the ability of macrophages to communicate to sensory neurons and partially prevented prolonged pain-like behaviors, more research is needed to determine if similar methods can be safely used to target human macrophages.