Mind the gender gap?

25 Nov 2014  |  Print

Mind the gender gap?

Chronic pain is a highly individual experience. However, patterns are emerging and one of these relates to gender – it appears that there are important differences between men and women. Moreover, it is in the best interests of our patients that we understand these differences so that we can better treat chronic pain in both sexes.

Clinical pain

Many epidemiologic studies have examined the prevalence of pain in men and women. A review of these studies found that the prevalence of chronic pain was consistently higher among women than men.[1] For example, in a study of >42,000 individuals in 17 countries, the prevalence of chronic pain conditions in the previous 12 months was 45% in females, but only 31% in males.[2]

In this study, the size of the prevalence gap between sexes was large. In other studies, the size of the difference was generally smaller, and was not always statistically significant, but the direction of the trend was remarkably consistent – towards greater chronic pain prevalence in females.[1]

Furthermore, the difference has been observed across multiple chronic pain conditions, including back pain, musculoskeletal pain, osteoarthritis, neuropathic pain and migraine.[3] It is also consistent across age groups.[2]

Interestingly, although chronic pain prevalence is clearly greater among women, pain severity is not so clearly demarcated. Several studies have reported greater pain severity among women, but others found no difference between treatment-seeking males and females.[4] It is not yet clear whether this reflects a genuine lack of difference between genders, or whether other factors (eg, selection biases in the studies) may have masked an effect.[4]

Experimental pain models

The epidemiologic data raise an important question: do sex differences in clinical pain reflect underlying differences in how pain is processed that put females at higher risk?

This has been investigated using a wide variety of pain stimuli in experimentally-induced pain models. These have included mechanical (eg, blunt pressure), electrical, thermal, ischemic and chemical stimuli (eg, capsaicin).[4]

The typical pattern observed in these studies is that women show greater sensitivity than men across the different types of pain stimuli.[4] However, the magnitude and statistical significance of these effects vary across different measures, and between studies.[4,5]

Differences in pain inhibition have also been examined experimentally using ‘endogenous pain modulation’ – a laboratory assessment of how effectively an individual’s pain inhibitory systems are functioning. A meta-analysis of studies using this measure showed that pain inhibition is typically more efficient in males than in females.[6]

The majority of experimental model studies were performed in healthy young adults. However, there is also evidence from pain patients. For example, in a recent study of patients with knee osteoarthritis, men had a higher pressure pain threshold and higher heat pain threshold and tolerance than women, at both the affected knee and at other sites away from their clinical pain.[7]

Mechanisms underlying sex differences

Although it is now established that there are sex differences in pain, the underlying mechanisms are not entirely clear. However, it is likely that both biological and psychosocial factors play a role.[4]

Biological factors may include the following[4]:

  • The influence of sex hormones – Testosterone appears to be more anti-nociceptive and protective than progesterone. Indeed, decreased androgen concentrations in men are associated with chronic pain.
  • Differences in the endogenous opioid system – There are differences between men and women in pain-related activation of brain mu-opioid receptors. The interaction of this system with sex hormones could be important in gender differences in pain sensitivity.
  • Genotype – Several genes have been linked with sex-dependent pain modulation. For example, two variant alleles of the melanocortin-1 receptor gene (more typically associated with red hair and fair skin) have been linked with greater analgesic responses in women who have the allele relative to men and to women who do not.

There are also various psychosocial factors that may be important[4]:

  • Pain coping strategies – These differ between genders. Men tend to use behavioral distraction and problem-focused tactics to manage pain. In contrast, women usually prefer techniques that are focused on social support, positive self-statements, and cognitive re-interpretation.
  • Catastrophizing and self-efficacy – Catastrophizing (the magnification and rumination of pain-related information) is associated with pain and is more common among women. In contrast, self-efficacy (the belief that one can successfully perform a behavior to achieve a desired goal) is associated with lower levels of pain and is more typical of men.
  • Sociocultural beliefs – In many societies, pain expression is considered more socially acceptable among women than men. This may lead to biased reporting of pain between genders.

Conclusions

Evidence shows that the prevalence of chronic pain is greater among women. Furthermore, in experimental pain models, females typically show greater pain sensitivity and lower pain inhibition than males. Multiple bio-psychosocial mechanisms appear to contribute to these differences.

Should this affect how we treat our patients? Possibly, although much work remains to be done. If we can better understand the differences in chronic pain between genders, we can better decide whether sex-specific tailoring of treatment is necessary in future.

References:

1. Fillingim RB, King CD, Ribeiro-Dasilva MC, Rahim-Williams B, Riley JL 3rd. Sex, gender, and pain: a review of recent clinical and experimental findings. J Pain 2009;10:447-485.

2. Tsang A, Von Korff M, Lee S, et al. Common chronic pain conditions in developed and developing countries: gender and age differences and comorbidity with depression-anxiety disorders. J Pain 2008;9:883-891.

3. Mogil JS. Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon. Nat Rev Neurosci 2012;13:859-866.

4. Bartley EJ, Fillingim RB. Sex differences in pain: a brief review of clinical and experimental findings. Br J Anaesth 2013;111:52-58.

5. Mogil JS. Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon. Nat Rev Neurosci 2012;13:859-866.

6. Popescu A, LeResche L, Truelove EL, Drangsholt MT. Gender differences in pain modulation by diffuse noxious inhibitory controls: a systematic review. Pain 2010;150:309-318.

7. Fillingim RB. Sex differences in clinical and experimental pain among younger and older adults. Presented at: 15th IASP World Congress on Pain; 6-11 October 2014; Buenos Aires, Argentina; Abstract TW021.

 

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