Genetics May Explain Why Women Are More Likely to Have Chronic Pain

By Pat Anson, PNN Editor

It’s no secret that women are far more likely than men to experience fibromyalgia, migraine, osteoarthritis and other chronic pain conditions. Why that is has been linked to everything from gender bias in healthcare to childhood trauma to women “catastrophizing” about their pain.  

A new study published by UK researchers in PLOS Genetics suggests that part of the reason is genetic differences between men and women.

In the largest genetic study of its kind, researchers at the University of Glasgow looked for genetic variants associated with chronic pain in over 209,000 women and 178,000 men who donated their medical and genetic data to the UK Biobank.

The researchers also investigated whether the activity of those genes was turned up or down in tissues commonly involved with chronic pain.

They found that 37 genes in men and 30 genes in women were active in the dorsal root ganglion, a cluster of nerves in the spinal cord that transmit pain signals from the body to the brain.

The findings support previous work by the same research team, which found that chronic pain originates to a large extent in the brain, and to a lesser degree in parts of the body where people “feel” pain. The study also suggests genetic differences between men and women may affect the immune system and how the two sexes respond to medication.

“Overall, our findings indicate the existence of potential sex differences in chronic pain at multiple levels… and the results support theories of strong nervous system and immune involvement in chronic pain in both sexes,” wrote lead author Keira Johnston of the University of Glasgow. "Our study highlights the importance of considering sex as a biological variable and showed subtle but interesting sex differences in the genetics of chronic pain."

Gender Bias

While genetic differences may partially explain why women are more likely to feel pain than men, gender biases may explain why they are treated differently, according to another study recently published in the Journal of Pain.

Researchers at the University of Miami found that when volunteers observed male and female patients expressing the same amount of pain, they had a tendency to view female patients' pain as less intense and more likely to benefit from psychotherapy.

The study consisted of two experiments in which adult volunteers were asked to view videos of men and women who suffered from shoulder pain. The videos came from a database of real patients experiencing different degrees of pain, and included their self-reported pain levels when moving their shoulders in a series of exercises.

The volunteer observers were asked to gauge the amount of pain they thought the patients in the videos experienced. They were also asked how much pain medication and psychotherapy they would prescribe to each patient, and which of the treatments they thought would be more effective.

The study found that female patients were perceived to be in less pain than the male patients — even when they reported and exhibited the same pain levels. Researchers believe those perceptions were partially explained by gender-based stereotypes.

"If the stereotype is to think women are more expressive than men, perhaps 'overly' expressive, then the tendency will be to discount women's pain behaviors," said co-author Elizabeth Losin, PhD, assistant professor of psychology at the University of Miami.

"The flip side of this stereotype is that men are perceived to be stoic, so when a man makes an intense pain facial expression, you think, 'Oh my, he must be dying!' The result of this gender stereotype about pain expression is that each unit of increased pain expression from a man is thought to represent a higher increase in his pain experience than that same increase in pain expression by a woman."

The volunteer observers were also more likely to choose psychotherapy as a treatment than pain medication for the female patients.

Interestingly, the gender of the observers did not influence pain estimation. Both men and women interpreted women's pain to be less intense.

"I think one critical piece of information that could be conveyed in medical curricula is that people, even those with medical training in other studies, have been found to have consistent demographic biases in how they assess the pain of male and female patients and that these biases impact treatment decisions," said Losin.

"Critically, our results demonstrate that these gender biases are not necessarily accurate. Women are not necessarily more expressive than men, and thus their pain expression should not be discounted."

Does Discrimination Cause Blacks to Feel More Pain?

By Pat Anson, PNN Editor

Racial and ethnic bias is a fact of life that impacts almost every aspect of our society – and healthcare is no exception. Research has shown that African-Americans are more likely to be undertreated for pain compared to white Americans, and that blacks are less likely to be prescribed opioid pain medication than whites.

Part of that stems from a false belief that there are biological differences between blacks and whites that cause African-Americans to feel less pain.

New research published in the journal Nature Human Behaviour disputes that stereotype, suggesting that African-Americans experience more pain due to the lasting effects of discrimination and other stressful life experiences.

In a small study led by researchers at the University of Miami, 28 African-Americans, 30 Latinos and 30 whites were subjected to a series of painful heat tests on their forearms while undergoing MRI brain scans.

The African-Americans not only rated their pain more intense and unpleasant than the other two groups, but the MRI’s found that the parts of their brains that process pain signals became more active than their counterparts’ as the temperature of the heat probes increased.

“There's evidence that both the general public and clinicians believe that African Americans are less sensitive to pain than non-Hispanic whites; yet research, including our own, shows exactly the opposite." said lead author Elizabeth Losin, PhD, an assistant professor of psychology at the University of Miami.  "Minorities, particularly African Americans, actually report more pain."

Losin began her research eight years ago while at the University of Colorado, recruiting volunteers in the Denver area. In addition to the heat tests and MRI scans, all participants completed questionnaires about various aspects of their lives, including unfair social treatment, discrimination and their trust in doctors.

Using the MRI brain scans, Losin and her colleagues identified two areas of the brain, the ventral striatum and ventromedial prefrontal cortex, which responded to pain more strongly in African Americans than the other two groups. Prior research has found that these two brain regions also respond more to pain signals in chronic pain patients.

“Our findings suggest that the link between chronic pain and ethnic differences in pain sensitivity may lie in the chronic stress associated with discrimination. Discrimination has been consistently associated with chronic stress and other adverse health outcomes in AA (African Americans) and other minority groups,” Losin wrote.

“It is also plausible that the higher pain sensitivity we and others have observed in AA compared to WA (White Americans) participants may be related to previous negative experiences with medical care in particular, which are more common in AA compared to non-Hispanic WA populations.”

Previous studies have found that childhood trauma, domestic violence and other stressful life situations can also increase the likelihood of chronic pain – so this new research does not prove that discrimination alone contributes to the increased risk of pain. Nevertheless, it lays the groundwork for future studies on the relationship between pain and discrimination.

"These findings exemplify how neuroimaging is teaching us that there are multiple contributions to pain," said co-author Tor Wager, PhD, a professor of neuroscience at Dartmouth College. "We need to consider the broader psychological and cultural setting when we think about what is underlying pain and how to address it."

Losin is continuing her research by studying the relationship between patients' trust in their doctors and their experience with pain.

"It's a common misconception that any difference you see between groups of people must be an intrinsic difference, rooted in our biology. But the differences we found in this study were related to people's life experiences," she said. "It reaffirms our similarities and provides hope that racial and ethnic disparities in pain can be reduced."