A new study conducted recently by a UTM and McGill research team has found that males remember earlier painful experiences more clearly than women. The study, “Male-specific conditioned pain hypersensitivity,” was recently published in the scientific journal Current Biology, and details how the memory of pain influences the future of pain perception to a higher extent in males. Last week, The Medium discussed the study in detail with Dr. Loren Martin, lead author of the published study and an assistant professor in psychology at UTM.

When asked as to how the study was conducted, Martin explains that in his lab, “[they] typically examine how mice react to different painful stimuli.” In this particular study, Martin and his team “place[d] [the mice] on a glass surface and [shone] a light on their feet which warm[ed] up the glass.” When the glass reached a certain temperature, the mice moved their paws away as soon as they felt a certain level of discomfort.

Because their goal was to “study how experiencing multiple and different types of pain would influence one pain over the other,” the team “injected a very dilute amount of acetic acid—which is vinegar—into the [mouse’s] belly.” The vinegar caused the mouse to experience a stomach ache. If the hot light was shone on the mice’s feet after inducing the stomach ache, Martin’s lab “found that [the male and female mice] became much more sensitive” to the hot light and moved their paw away quicker. 

The surprising results were discovered when Martin “[brought] the mice back into the environment in which they had undergone that vinegar injection.” Martin details how the “male mice showed a hypersensitive response [meaning that] they reacted much quicker to shining that light on their foot,” while for female mice, “it was just like they had not undergone that vinegar injection [as] they were not hypersensitive.” For the male mice, the hypersensitivity lasted at least a few days.

Martin concluded that memory was involved because if the male mouse was placed in an environment different to where it had received the discomforting vinegar injection, it did not show a hypersensitive response to the pain-inducing hot light. The hypersensitive response was only displayed “in the pain-associated context.” Martin believes that the male mice “learned that the environment [was] associated with a painful experience, [and therefore] were anticipating that pain making [the male mice] more responsive and hypersensitive when the lab shone that light on the [male mice’s] feet.”

What’s also interesting is that when Martin’s lab replicated the study in people, they found similar results. Martin’s lab applied a tiny probe on each participant’s forearm, heated the probe up, and kept the probe on there for about a minute. After a minute, Martin “ask[ed] people to rate how painful they thought that was on a scale of 0 to 100, with 0 being not at all, and 100 being the worst imaginable pain.”

Martin states that “on average, most people will rate [the pain] about 40 out of a 100.” Following the probe application, Martin’s lab brought the people back and attached a blood pressure cuff to the arm and increased the pressure “to more than when you have your blood pressure taken for twenty minutes,” because they “wanted to investigate memory, and whether or not experiencing a long-lasting pain in a particular environment would influence subsequent pain responses.” The researchers furthermore asked individuals “to flex their hands to try and increase blood flow which [made] it even more discomforting.”  The next day, people either were brought back to the same environment where the blood pressure cuff increase was administered or “a completely different environment with a different experimenter, in a different building, and in a different room.” As observed in mice, “when men went back to that same blood pressure environment, they reported that same [probe] as being more painful!” The men’s pain rating “went from 40 to 45 out of 100 to almost 60 out of a 100 which is a pretty big change.”

A drug was administered to the mice following the experiment to erase their memory in order to block out the negative pain memory. When asked as to whether a similar drug could be used in humans, Martin replies that it is possible; however, researchers would have to “develop a strategy where [one] could selectively erase the pain associated memory, fear, or a traumatic experience,” as the drug used in mice erased their entire memory. Martin comments that for a drug which would erase painful memories, more research on “what neurons and what neural circuit might be responsible specifically for painful memories” is required.

Martin’s influential study is inspired by his Ph.D. and background in memory and synaptic plasticity. For his post-doctoral work, he started working in a pain lab where he noticed that many of “the molecular mechanisms underlying pain and memory ended up being the same thing.” Martin was “interested in eventually bridging the two” and “was curious” as he thinks “most people don’t really have memory for pain and painful experiences.” He says this study “point[s] that [individuals] might not have this very good explicit recall of memory but physiologically, and maybe implicitly, [the] body may be actually quite attuned to [the memory of the pain].”

Martin says he was highly surprised at the sex difference in the responses to pain. He explains how he was aware that, due to sex hormones, “as a whole, females are more sensitive to pain:” however, was still astonished when the results of this study suggested that the memory associated with pain has a more prominent effect in males. Martin points out the importance of using both male and female mice in experiments, as with mouse research, most people only study males, and if he had only used male mice, he “would have found the effect” however, the problem would be that “he wouldn’t have understood or even discovered that it’s not true for females.”

Moving forward, Martin and his lab will be “doing a number of things, specifically, going more mechanistic with it—which brain mechanisms are involved, what’s happening with the neurons, [and if it’s possible] to disentangle pain memories from the good memories.” Martin describes “a newer branch of research which stems from this, [which] is how [individuals] learn pain, especially chronic pain.” He describes how “one of the prevailing theories is that chronic pain does not go away, because [individuals] have learned the pain” and that “one of the things that [his team and him] are planning to do in the future, is to look at whether being more intelligent makes you more susceptible to chronic pain.”

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