Why Women Feel More Pain: Groundbreaking Study Reveals Key Biological Clue

Researchers at the University of Calgary have uncovered biological differences between the sexes in how chronic pain is experienced.

A new study led by Dr. Tuan Trang, a professor at the University of Calgary, offers insight into why women are disproportionately affected by chronic pain. According to a 2019 report from the Canadian Pain Task Force, chronic pain is more common in females across all age groups, including children, compared to males.

“Both males and females experience pain, but the biological pathways they use are different,” explains Trang, who holds appointments in the Faculty of Veterinary Medicine and the Cumming School of Medicine. “Our study identifies a unique immune-cell-driven process that differs between the sexes.”

Neuropathic Pain and Allodynia Explained

Published in Neuron, the research focused on neuropathic pain, a type of pain caused by damage to the nerves or nervous system. One particularly difficult-to-treat symptom of neuropathic pain is allodynia, where non-painful stimuli like light touch, mild temperatures, or even clothing can cause severe pain.

Using rodent models, the researchers found that in both male and female animals, pain signals travel through pannexin 1 (Panx1) channels. However, the type of immune cell involved in that signaling differs by sex. In females, activating Panx1 also triggers the release of leptin, a hormone linked to increased pain sensitivity, helping explain why women may be more vulnerable to chronic pain.

“Injury to a nerve can be debilitating,” says Trang. “We know that a lot of preclinical research has been in male subjects. Consequently, treatments were often developed from a male-based understanding and may not be very effective in females.”

Leptin’s Link to Female Pain Sensitivity

Heightened levels of leptin in females experiencing chronic pain have been recorded in studies before. Trang notes that as far back as the 1980s, researchers who were working with human blood samples found that female patients experiencing chronic pain had higher levels of leptin in their blood than those who did not have chronic pain.

“In the clinic, we’ve known for many years that women are more likely than men to suffer from chronic pain, and it’s often hard to know why some people respond to treatment and others don’t,” says Dr. Lori Montgomery, MD ‘03, pain clinician and clinical associate professor at the CSM. “Both sex and gender are important factors that need a lot more investigation, but this latest research might prove to be one of the ways that we can personalize treatment for patients so that it’s more likely to be effective.

Reference: “Divergent sex-specific pannexin-1 mechanisms in microglia and T cells underlie neuropathic pain” by Churmy Y. Fan, Brendan B. McAllister, Sierra Stokes-Heck, Erika K. Harding, Aliny Pereira de Vasconcelos, Laura K. Mah, Lucas V. Lima, Nynke J. van den Hoogen, Sarah F. Rosen, Boram Ham, Zizhen Zhang, Hongrui Liu, Franz J. Zemp, Regula Burkhard, Markus B. Geuking, Douglas J. Mahoney, Gerald W. Zamponi, Jeffrey S. Mogil, Shalina S. Ousman and Tuan Trang, 31 January 2025, Neuron.

Funding: Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Donna and Rod Evans