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Pain is sexist. Sex Hormones and Anxiety Modulate Brain Responses to Painful Stimuli



The 2024 Global Year will examine what is known about sex and gender differences in pain perception and modulation and address sex-and gender-related disparities in both the research and treatment of pain.

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Serge Marchand, Ph.D. and Isabelle Gaumond, Ph.D.

Women and men are different in many ways; some of these differences are obvious and some not so intuitive.  For example, pain is sexist.  The burning question is who between men and woman is more tolerant to pain?  For most people, it seems clear that women are more tolerant or at least they complain less than men.  You just have to think about the complain coming from the famous «men’s cold».  Based on this observation, one will conclude that men would never be able to tolerate childbirth.

Surprisingly, when we look at experimental pain we found that women have a lower pain threshold and perceive a stimulus of the same intensity as more painful than men[1].  Interestingly, the same results are also found in rats.  Female rats have lower threshold than male.  However, this sex difference is absent before puberty in human[2] and after gonadectomy (castration in male and ovariectomy in female) in rats[3].  These results suggest an important role of sex hormones in pain perception.  Moreover, women are overrepresented in almost all chronic pain conditions.

When we try to understand the mechanisms by which sex hormones play a role in pain, we must first understand that pain is a complex phenomenon resulting from a balance between endogenous excitatory and inhibitory mechanisms. Interestingly, when comparing ovariectomized females with intact females, we observed that female sex hormones, estrogen and progesterone, reduce the efficacy of inhibitory mechanisms. For their part, castrated males have excitatory pro-nociceptive mechanisms are more activated than those of intact males, suggesting that testosterone might be protective against pain.   The same seems to be true in human.  During the menstrual cycle, the only significant modulation we found with experimental pain was for the inhibitory mechanism that was significantly higher during the ovulatory phase as compared to the other phases.

Nevertheless, sex hormones are far from being the only actors playing a role in pain perception.  Indeed, anxiety and mood are also important factors.  In a recent study, we assessed pain-related brain activity in healthy men and women.  We found that the difference in response between the two sexes is largely related to anxiety responses[4].  Dispositional (trait) anxiety affects baseline pain sensitivity scores and contributes to sex differences in pain.  However, although the level of anxiety was lower in men, the close relationship between situational (state) anxiety and pain was only observed in men!  Interestingly, the same is true for autonomic responses; men present a positive correlation between pain intensity and sympathetic activity while it is not the case for women[5].

One can postulate that phylogenetically, women have a heightened perception of their environment, using hearing, taste, smell and even pain in order to protect their progeny from a potential threat.  For their part, men had more to deal with situations where nociceptive messages had to be ignored, such as during hunting.  But what about childbirth?  It seems that nature thought of that too.  Pain threshold is significantly higher during pregnancy, most probably because there are important hormonal changes during this phase[6].

It is always fun to speculate about male-female differences based on evolution, even if we don’t really know what it’s all about!  Most importantly, these findings tell us that men and women are different in the face of pain and that we should take in account these differences in our search for better treatments.

Dr Marchand

Dr. SERGE MACHAND, Ph.D., Prof. of Medicine at Univ. de Sherbrooke, is the Director of the centre de recherche clinique Étienne-Le Bel of the Sherbrooke University hospital (CRCELB-CHUS). He received his PhD in Neuroscience from Université de Montréal in 1992 and then completed his post-doctoral training in neuroanatomy at the University of California in 1994.  He is the author of several articles and book chapters in the field of pain mechanisms and treatment.  His research is characterized by a close link between fundamental and clinical projects on the neurophysiological mechanisms implicated in the development and persistency of chronic pain.



1. Fillingim, R., King, C., Ribeiro-Dasilva, M., Rahim-Williams, B., & Riley, J. (2009). Sex, Gender, and Pain: A Review of Recent Clinical and Experimental Findings The Journal of Pain, 10 (5), 447-485 DOI: 10.1016/j.jpain.2008.12.001

2. Robinson JE, & Short RV (1977). Changes in breast sensitivity at puberty, during the menstrual cycle, and at parturition. British medical journal, 1 (6070), 1188-91 PMID: 861531

3. Gaumond, I., Arsenault, P., & Marchand, S. (2002). The role of sex hormones on formalin-induced nociceptive responses Brain Research, 958 (1), 139-145 DOI: 10.1016/S0006-8993(02)03661-2

4. Goffaux P, Michaud K, Gaudreau J, Chalaye P, Rainville P, & Marchand S (2011). Sex differences in perceived pain are affected by an anxious brain. Pain, 152 (9), 2065-73 PMID: 21665365

5. Tousignant-Laflamme Y, & Marchand S (2006). Sex differences in cardiac and autonomic response to clinical and experimental pain in LBP patients. European journal of pain (London, England), 10 (7), 603-14 PMID: 16298532

6. Dawson-Basoa ME, & Gintzler AR (1996). Estrogen and progesterone activate spinal kappa-opiate receptor analgesic mechanisms. Pain, 64 (3), 608-15 PMID: 8783328


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