Males remember previous pain clearly than females

Scientists increasingly believe that one of the driving forces in chronic pain--the number one health problem in both prevalence and burden--appears to be the memory of earlier pain. Research published in Current Biology suggests that there may be variations, based on sex, in the way that pain is remembered in both mice and humans.

The research team found that men (and male mice) remembered earlier painful experiences clearly. As a result, they were stressed and hypersensitive to later pain when returned to the location in which it had earlier been experienced. Women (and female mice) did not seem to be stressed by their earlier experiences of pain. The researchers believe that the robust translational nature of the results, from mice to men, will potentially aid scientists to move forward in their search for future treatments of chronic pain.

Creating memories of pain in humans and mice

In experiments with both 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 put in a testing container of a certain shape—depending on the species) where they experienced low levels of pain caused by heat delivered to their hind paw or forearm. Humans rated the level of pain on a 100-point scale and mice “rated” the pain by how quickly they moved away from the heat source. Immediately following this initial experience of low-level pain, subjects experienced more intense pain designed to act as Pavlovian conditioning stimuli. The human subjects were asked to wear a tightly inflated blood pressure cuff and exercise their arms for 20 minutes. This is excruciating and only seven of the 80 subjects rated it at less than 50 on a 100-point scale. Each mouse received a diluted injection of vinegar designed to cause a stomach ache for about 30 minutes.

In order to look at the role that memory plays in the experience of pain, the following day the subjects returned to either the same or a different room, or to the same or a different testing container. Heat was once again applied to their arms or hind paws.

When (and only when) they were taken into the same room as in the previous test, the men rated the heat pain higher than they did the day before, and higher than the women did. Similarly, male, but not female mice returning to the same environment exhibited a heightened heat pain response, while mice placed in a new and neutral environment did not.

“We believe that the mice and the men were anticipating the cuff, or the vinegar, and, for the males, the stress of that anticipation caused greater pain sensitivity,” says Mogil. “There was some reason to expect that we would see increased sensitivity to pain on the second day, but there was no reason to expect it would be specific to males. That came as a complete surprise.”