Let’s talk about sex!   December 4th, 2023

Let’s talk about sex, baby (1). Or maybe not? Let’s talk about gender!

To talk about gender, I will start with some definitions so we speak the same language.

First of all, ‘gender’ is not a synonym for ‘sex’. Sex refers to the genetic sex assigned at birth (male, female, intersex) (2), while gender can be further divided into ‘gender identity’ and ‘gender expression’. Gender identity is defined as an individual’s internal experience of one’s own gender (cis*, trans**, gender diverse, other) (3,4). Whereas gender expression is the external or behavioural expression of one’s gender, which may or may not be in line with one’s gender identity (3,4). Another important, but different term is ‘sexual orientation’ which refers to one’s romantic and/or sexual orientation (gay, lesbian, bi, pan, asexual, etc.) (4).

Binomial sex differences (male/female) have been studied very widely within pain research whereby women tend to be more sensitive to pain than men (5) In laboratory settings, quantitative sensory testing (QST) is frequently used to assess these sex differences. Nowadays these results are more and more debated. A first clarification might be that a binomial division is not an accurate reflection of the entire population, as intersex people are not mentioned despite their 1.7% estimated prevalence (4). Another reason is that the sex assigned at birth cannot fully explain the differences in pain experience we find between men and women. That is where the concept of ‘gender’ should be introduced.

An interesting study of Strath et al. (2020) examined differences in pain responses between cisgender and transgender individuals with HIV and chronic pain. The participants were subjected to a QST protocol including assessment of the heat pain threshold, heat pain tolerance, temporal summation of heat pain, temporal summation of mechanical pain, and conditioned pain modulation. Their results showed a greater magnitude of temporal summation for heat pain stimuli or mechanical stimuli in transgender women and cisgender women compared with cisgender men (6). Additionally, transgender women and cisgender women reported greater chronic pain severity compared with cisgender men (6). These results suggest that gender identity may play a more important role in pain sensation than the sex assigned at birth. If we extrapolate these results towards the higher prevalence of central sensitization and associated secondary hyperalgesia in people with a female sex assigned at birth (7), we can carefully suggest that transgender women may be at risk for central sensitization and subsequent chronic pain. A noteworthy limitation in the study of Strath et al. (2020) is that hormone status was not examined although other research suggests that hormones affect the mediation of chronic pain (8).

Another interesting study of Levit et al. (2021) assessed the prevalence of fibromyalgia, a central sensitization syndrome, in transgender individuals. They found a 14.8% prevalence of fibromyalgia in the general transgender population whereas this was only 2.5% in the overall population (8). Opposite to what we expected, fibromyalgia was more prevalent in transgender men (19.4%) compared to transgender women (7.0%) (8). Levit et al. (2021) assumes that early in-utero hormone-dependent central nervous system development may have life-long effects and thereby can still be relevant in transmen. So this presumption questions the previously mentioned hypothesis.

To date, there are few studies that examine the role of gender identity in pain experience, also taking into account the influence of hormone therapy (8). Furthermore, these studies all investigate a transgender population. Scarcely any study on other gender diverse people, for example non-binary people, has been performed.

When examining pain sensitivity, future research should include gender as a variable and not only the sex assigned at birth to help us unravel differences in experimental and clinical pain. However, we still have a long way to go.

But for now, let’s talk about gender, baby.

* Cisgender: one’s gender identity corresponds with one’s sex assigned at birth

** Transgender: one’s gender identity is incongruent with one’s sex assigned at birth

Elise Cnockaert

2023 Pain in Motion

References and further reading:

1. Salt-N-Pepa. Let’s Talk About Sex (0:21). 1991.

2. Auer MK, Liedl A, Fuss J, Nieder T, Briken P, Stalla GK, et al. High impact of sleeping problems on quality of life In transgender individuals: A crosssectional multicenter study. PLoS One. 2017 Feb 1;12(2).

3. Boerner KE, Chambers CT, Gahagan J, Keogh E, Fillingim RB, Mogil JS. Conceptual complexity of gender and its relevance to pain. Vol. 159, Pain. Lippincott Williams and Wilkins; 2018. p. 2137–41.

4. Transgender Infopunt. Transgenderinfopunt.be [Internet]. [cited 2023 Aug 11]. Available from: https://www.transgenderinfo.be/nl

5. Mogil JS. Sex differences in pain and pain inhibition: Multiple explanations of a controversial phenomenon. Vol. 13, Nature Reviews Neuroscience. 2012. p. 859–66.

6. Strath LJ, Sorge RE, Owens MA, Gonzalez CE, Okunbor JI, White DM, et al. Sex and gender are not the same: Why identity is important for people living with HIV and chronic pain. J Pain Res. 2020;13:829–35.

7. Jensen MT, Petersen KL. Gender differences in pain and secondary hyperalgesia after heat/capsaicin sensitization in healthy volunteers. Journal of Pain. 2006 Mar;7(3):211–7.

8. Athnaiel O, Cantillo S, Paredes S, Knezevic NN. The Role of Sex Hormones in Pain-Related Conditions. Vol. 24, International Journal of Molecular Sciences. MDPI; 2023.