Sex differences in pain

January 17th, 2022

Written by: Lindsay Ejoh

20% of adults in the United States, or roughly 50 million people, suffer from chronic pain disorders- and the majority of these are women. Emerging research shows that the underlying mechanisms of pain perception differ between males and females (see aside for an in-depth explanation of sex and gender). This applies for the two types of pain: acute pain, like the short-term pain of a pinprick or a burn, and chronic pain disorders that last much longer, such as fibromyalgia, osteoarthritis, migraine, inflammatory bowel syndrome, and lower back pain, etc1. As a result, females tend to have higher sensitivity to acute pain, and have a greater risk of developing chronic pain disorders.

Aside: Sex and Gender

Sex and gender are often used interchangeably, but they are not the same thing. Sex refers to biological factors like genetics, sex hormones, and physiology that differ between people who are male, female, or intersex. Gender, on the other hand, is a social construct that assigns expectations, behaviors, and stereotypical roles associated with being a man or a woman2. This article focuses on sex differences in pain between males and females, since all the research conducted in this area has considered sex as a binary3. However, there are sexes that exist outside of male and female, just like how there are genders that exist outside of man and woman.

Do males and females rate their pain differently?

Pain, like many other human experiences, is subjective. If your doctor asks you to rate your pain from 1-10, your “10” may be another person’s “4.” Regardless, human studies on acute pain have shown females have higher pain sensitivity than males, and that males are better at tolerating their pain4. This is reflected in animal studies as well, where pain levels are not determined by a verbal score, but instead by objectively observing how often pain behaviors are exhibited by an animal experiencing pain. These pain behaviors include facial grimaces, licking the injured area, jumping to escape a painful environment, etc5. Additionally, human females are more likely to take an anxious approach to chronic pain, feeling helpless in controlling it, and tend to catastrophize their pain and perceive their pain as a more serious threat than males4.

Pain sensitivity differs among sexes- but what factors underlie this? There are biological, psychological, and social factors that contribute to this phenomenon.

Impact of the immune system on sex differences in chronic pain

The immune system can heavily influence pain perception through microglia, the immune cells of the nervous system6. Microglia identify and get rid of foreign pathogens, as well as aid in growth and healing of nerve cells. Mice born without microglia are less sensitive to pain from a nerve injury- but this is only seen in male, not female mice7. Therefore, microglia seem to promote pain hypersensitivity- though only in males. This might be a basis for why sex differences in pain sensitivity are found in humans, though further work must be done exploring impact of microglia in this phenomenon in humans. Expanding what we know about the impact of the immune system on other chronic pain disorders in rodents and humans, as well as chronic pain disorders outside of nerve injuries, remains an objective of the pain research community.

Psychosocial impact

Gender roles may contribute to the way we cope with our pain. Men in western societies are often socialized to show less of a reaction to pain than women, which may influence perceived sex differences. Masculine gender norms lead to increased tolerance of pain among men, while feminine gender norms encourage stronger reactions to pain in women. These socialized differences may contribute to the sex differences in pain that we see in human research and may also contribute to gender discrimination in pain treatment and assessment in the clinic.

Conclusion

It is important to note that this research does not encompass all sexes, for example intersex people, that do not fall cleanly into either sex, and instead fall on a spectrum depending on their hormone levels, genetics, anatomy, etc., are estimated to comprise about 1.7% of the population8. There is also little to no data to indicate how pain responses change when someone undergoes sex-changing surgery or a gender-affirming hormone treatment. However, the existing and future work investigating the mechanisms and impact of sex differences in pain will help us understand why the experience of pain differs among individuals, and is critical to the development of better, more personalized treatments for pain.

References

  1. Bartley, E. J., & Fillingim, R. B. (2013). Sex differences in pain: a brief review of clinical and experimental findings. British journal of anaesthesia, 111(1), 52–58. https://doi.org/10.1093/bja/aet127
  2. Evans, L. T. and J. (2019, February 21). What is the difference between sex and gender? What is the difference between sex and gender? – Office for National Statistics. Retrieved January 10, 2023, from https://www.ons.gov.uk/economy/environmentalaccounts/articles/whatisthedifferencebetweensexandgender/2019-02-21
  3. Keogh E. (2022). Sex and gender differences in pain: past, present, and future. Pain, 163(Suppl 1), S108–S116. https://doi.org/10.1097/j.pain.0000000000002738
  4. Fillingim, R. B., King, C. D., Ribeiro-Dasilva, M. C., Rahim-Williams, B., & Riley, J. L., 3rd (2009). Sex, gender, and pain: a review of recent clinical and experimental findings. The journal of pain, 10(5), 447–485. https://doi.org/10.1016/j.jpain.2008.12.001
  5. Kimmey, B. A., McCall, N. M., Wooldridge, L. M., Satterthwaite, T. D., & Corder, G. (2022). Engaging endogenous opioid circuits in pain affective processes. Journal of neuroscience research, 100(1), 66–98. https://doi.org/10.1002/jnr.24762
  6. Augusto-Oliveira, M., Arrifano, G. P., Lopes-Araújo, A., Santos-Sacramento, L., Takeda, P. Y., Anthony, D. C., Malva, J. O., & Crespo-Lopez, M. E. (2019). What Do Microglia Really Do in Healthy Adult Brain?. Cells, 8(10), 1293. https://doi.org/10.3390/cells8101293
  7. Mapplebeck, J. C. S., Beggs, S., & Salter, M. W. (2016). Sex differences in pain: a tale of two immune cells. Pain, 157 Suppl 1, S2–S6. https://doi.org/10.1097/j.pain.0000000000000389
  8. Director, M. C. A., Coleman, M., Director, A., Director, J. P. S., Parshall, J., Director, S., Gordon Director, P., Gordon, P., Director, Medina, C., Gruberg, S., Buchanan, M. J., Banks, L., Khattar, R., & Correa-Buntley, T. (2022, August 22). Key issues facing people with intersex traits. Center for American Progress. Retrieved January 11, 2023, from https://www.americanprogress.org/article/key-issues-facing-people-intersex-traits/#:~:text=It%20is%20estimated%20that%20up,identifiable%20sexual%20or%20reproductive%20variations

Cover image obtained from Wikimedia Commons by Robert Weis

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