For decades, women suffering from chronic pain have been told “it’s all in your head” when treatments that work for men fail them. Now, research from the University of Calgary reveals that women’s pain actually operates through entirely different biological pathways than men’s. Scientists have discovered that the same protein triggers pain in both sexes, but through completely different immune cells and chemical signals.
A new study published in Neuron reveals that a protein called pannexin-1 (or Panx1 for short) works differently in males and females. This helps to explain why women are more likely to develop chronic pain conditions and why they often don’t respond as well to certain treatments.
The Divide in Pain Research
Most pain research has historically focused on male subjects, even though women make up the majority of chronic pain patients. This study aims to fix that imbalance by looking at both male and female animals to understand why pain works differently between sexes.
While both sexes use the Panx1 protein in their immune cells to create pain signals, they use completely different cells and chemical messengers to do it.
In males, Panx1 works through cells called microglia (the immune cells of the spinal cord and brain) to release a protein called VEGF, which increases pain sensitivity. In females, however, Panx1 works through CD8+ T cells (a type of white blood cell) to release leptin, a hormone best known for its role in hunger and metabolism. This may help explain why treatments that target microglia cells work well for reducing pain in males but often fail in females.
Crossing Biological Boundaries
When they took microglia cells from male animals, activated them, and transferred them into females, the females developed pain. Similarly, when they transferred activated female T cells into males, the males also developed pain. This confirmed that these sex-specific mechanisms weren’t just correlations; they actually cause pain.
The researchers also created mice that lacked the Panx1 protein specifically in microglia cells. Male mice without this protein showed much less pain after nerve injury, while female mice still developed normal pain sensitivity.
When they analyzed fluid from the spinal cord, they found that after nerve injury, males had higher levels of VEGF while females had higher levels of leptin. Blocking VEGF reduced pain in males but not females, while neutralizing leptin reduced pain in females but not males.
Hope for Better Pain Treatments
This could lead to better pain treatments for everyone. Current treatments for neuropathic pain (pain caused by nerve damage) include anticonvulsants, antidepressants, and opioids. These treatments tend to work less effectively in women and often cause worse side effects.
With this new knowledge, doctors might eventually be able to prescribe treatments targeted specifically to each sex, like VEGF blockers for men and leptin blockers for women.
This discovery is particularly important for conditions like fibromyalgia, which affects women much more often than men. Previous studies have shown that leptin levels can predict pain severity in women with fibromyalgia. This research now provides a possible explanation for that connection.
Panx1 could be a treatment target that works for both sexes. Although the way the body reacts to this protein is different for men and women, medications targeting it could help both, potentially transforming pain treatment.
For women who have struggled to have their pain taken seriously or effectively treated, this research provides solid evidence that treating female pain really may deserve specific research and targeted treatments. Doctors may eventually move beyond one-size-fits-all approaches to develop treatments tailored to each person’s unique biology.
Source : https://studyfinds.org/womens-pain-misunderstood-medication/
