Gender and Pain Tolerance


“I’m in pain, and I’m wet, and I’m still hysterical!”
Gene Wilder, The Producers.

“Yup. You’re a 7.” Scrubs. ABC Studios.
 
Since the dawn of time, men and women have been compared in nearly every regard. Lately, one of the debate topics has centered around pain. Specifically, pain tolerance. Are men better equipped to handle pain? Did you scoff at the last statement due to your own experience with childbirth? There’s a lot of hearsay and conjecture on this topic, but what has science discovered to this point?
Part of the inherent difficulty in assessing pain tolerance is its subjective nature. Human subjects have to report what their level of pain is, and this in and of itself can skew the results due to any number of biases. If you’re unfamiliar, there’s a simplistic pain chart that doctors refer to in order to evaluate a patient’s pain level.
Statistically, women are actually more at risk for chronic pain conditions like headaches, migraines, lower back, neck and knee pain. This doesn’t even take into consideration the conditions that are uniquely restricted to women (endometriosis, menstrual pain, etc.)1. In 2011, a study analyzed over 160,000 hospital-reported pain scores. 11,000 cases were documented for men and women with the same diagnosis, and overall, women were found to report higher pain scores than men2.
But wait, you’ve definitely experienced a male family member or loved one seemingly at death’s door anytime they’ve come down with a cold. In fact, some colloquially call this “man flu”, where men supposedly exaggerate their symptoms and seem helpless. Well, there may actually be scientific evidence to back this up. In a study published in the American Journal of Physiology, nasal cells were obtained from male and female donors. Cells were then pre-treated with estrogen or SERMs (estrogen receptor modulators). Female cells that received this treatment were more resistant to infection by influenza virus. However, male cells did not display this same resistance after treatment. So, this may demonstrate a sex-specific effect of estrogen that confers immune health3.
But, let’s get back to our topic at hand. Why do women seem to be more sensitive to pain? There are several reasons that could explain these observed trends1.
  • Estrogen levels: data has shown that estrogen can help suppress pain in women. At certain points of the menstrual cycle, women may have lower levels of estrogen, resulting in higher pain scores4.
  • Experience: Abuse, clinical pain frequency, and even labor pain could alter someone’s scale and scores.
  • Psychology: state of mind can amplify or negate some pain experiences. Anger, anxiety, fear, and other factors can influence pain reception.
  • Genetics: X or Y-linked chromosome genes could explain gender differences.
  • Neurochemicals: a variety of neurochemicals and their receptors may influence pain levels or receptiveness.
  • Machismo: Culturally, men can be expected to rub some dirt on their ailment and walk it off. This bravado can lead to men hiding their pain or reporting lower overall scores.

“We’re men...manly men...we roam around the forest looking for fights.” Robin Hood Men in Tights. 20th Century Fox.
Interestingly, some of the sexual dimorphisms in pain perception have been linked to differences in immune response. These observations are interesting, but are there any immunological explanations behind the differences we see? The research is still ongoing, but a few interesting studies have been published so far. For example, Jeffrey Mogil of McGill University found differences in TLR4 expression on microglia between male and female mice. In 2011, he found that male microglia from mice, but not female, was involved with pain processing signals. Female mice did not need microglia in order to feel nerve pain. Mogil then wanted to investigate whether female mice had alternative routes to process pain. So, he used female mice lacking all adaptive immune cells. When deprived of these cells, the female mice resorted to using microglia for the same pain pathway. If the female mice were treated with testosterone, they then switched their pain signaling preference to the use of microglia5.

Male and female pain pathways may operate on different mechanisms. New Girl. Fox Broadcasting.
These studies suggested that men seemingly have a higher pain tolerance than women. And, results like the ones from the TLR4/microglia experiment illustrate possible sex-linked immune mechanisms that alter how male and female genders might receive pain differently. This information also demonstrates just how important it is to maintain animal studies that involve both sexes. Even if a drug blocked TLR4 pain pathways with incredible efficacy in males, it would undoubtedly encounter difficulty or fail in female subjects who possess redundancy pathways that avoid microglia or TLR4. From 1996 to 2005, 79% of surveyed papers utilized only male rodents in their animal studies1. Some researchers may fear that the female oestrous cycle adds variability to their experiment. However, with sex-specific pain pathways, it’s quite clear both males and females must be considered for these types of studies.
As you can see, we covered a considerable amount of information that is conveniently condensed into one handy poster for your lab. Have any thoughts or questions on our newest poster? Send them to tech@biolegend.com.

Just when I thought I got the hang of science...
References:
  1. Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon
  2. Sex Differences in Reported Pain Across 11,000 Patients Captured in Electronic Medical Records
  3. Man flu might actually be real after all
  4. Studies suggest men handle pain better
  5. Sex differences in pain pathway
Contributed by Ken Lau, PhD.
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