Scientists increasingly believe that one of the driving forces in chronic pain, the number one health problem in both prevalence and burden, seems to be the memory of previous pain. The research published on Thursday in Current Biology suggests that there may be variations, based on sex, in the way pain is remembered in both mice and humans.
The research team, led by colleagues at the McGill and Toronto Mississauga universities in Canada, found that men (and male mice) clearly remembered previous painful experiences. As a result, they were stressed and hypersensitive to the subsequent pain when they returned to the place where they had previously experienced it.
The women (and the females) did not seem to feel stressed by their previous experiences of pain. The researchers believe that the robust translational nature of the results, from mice to men, will potentially help scientists advance their search for future treatments for chronic pain.
It was a discovery that totally surprised. "We set out to do an experiment to observe hypersensitivity to pain in mice and found these amazing differences in stress levels between male and female mice," explains the study's lead author, Jeffrey Mogil, professor of Pain Studies in the Department of Psychology of McGill and the Alan Edwards Center for Pain Research.
And he continues: "So we decided to extend the experiment to humans to see if the results would be similar." We were amazed when we saw that there seemed to be the same differences between men and women that we had seen in mice.
"What was even more surprising was that the men reacted more, because it is well known that women are more sensitive to pain than men and that in general they are also more stressed," explains Loren Martin, first author of the article and assistant professor of Psychology at the University of Toronto Mississauga.
In experiments with humans and mice, the subjects (41 men and 38 women between the ages of 18-40 in the case of humans) were taken to a specific room (or placed in a test container in a certain way, depending on the species) where they experienced low levels of pain caused by the heat that was supplied to the hind leg or forearm.
Humans rated the pain level on a scale of 100 points and the mice "rated" the pain by how quickly they moved away from the heat source. Immediately after this initial experience of low pain, the subjects experienced a more intense pain designed to act as Pavlovian conditioning stimuli.
Human subjects were asked to wear a tightly inflated blood pressure cuff and to exercise their arms for 20 minutes. This is unbearable and only seven of the 80 subjects scored less than 50 on a scale of 100 points. Each mouse received a diluted injection of vinegar designed to cause a stomach ache for about 30 minutes.
BLOCKING MEMORIES MAKES PAIN DISAPPEAR
To observe the role of memory in the experience of pain, the next day the subjects returned to the same room or to a different room, to the same room or to a different testing room. Once again heat was applied to his arms or hind legs.
When (and only when) they were taken to the same room as in the previous test, men rated pain from heat higher than the previous day and higher than women. Similarly, male mice, but not those that were female, that returned to the same environment showed a greater response to pain from heat, while rodents placed in a new and neutral environment did not.
"We believe that mice and men anticipated the cuff or vinegar and, for males, the stress of that anticipation caused greater sensitivity to pain," says Mogil, "there was a reason to expect us to see greater sensitivity to pain. second day, but there was no reason to expect it to be specific to men, that was a complete surprise. "
To confirm that the pain increased due to memories of previous pain, the researchers interfered in memory by injecting the brains of male mice with a medication called ZIP that is known to block memory. When the scientists performed the pain recall experiment, these mice showed no signs of pain recall.
"This is an important finding because there is increasing evidence to suggest that chronic pain is a problem as long as you remember it, and this study is the first time that it shows a memory of pain using a translation approach, both rodents as well as humans, "says Martin, who is also a Canadian Level II Research Professor in Translational Pain Research.
He adds: "If remembered pain is a driving force of chronic pain and we understand how pain is remembered, we can help some patients by directly treating the mechanisms behind the memories." "This research supports the idea that memory of pain can affect later pain," concludes Mogil.