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CALGARY, AB – A groundbreaking study led by Dr. Tuan Trang, Ph.D., at the University of Calgary, has uncovered a potential biological explanation for why women experience chronic pain more frequently than men, and why pain medications may not be equally effective for both sexes. The findings, published in the journal Neuron, suggest that sex-specific differences in immune cell responses play a crucial role in neuropathic pain.
Neuropathic pain, caused by nerve damage, often manifests as allodynia, a condition where normally non-painful stimuli become agonizing. The study, conducted on rodents, revealed that while both male and female subjects utilize pannexin 1 (Panx1) channels to transmit pain signals, they do so through different immune cell pathways.
“Both males and females develop pain, but each sex develops it through different means,” explains Dr. Trang, a professor in the Faculty of Veterinary Medicine and Cumming School of Medicine (CSM). “This study identifies a very unique type of biological process through a specific immune cell that is distinctive to each sex.”
A key discovery was the role of leptin in female rodents. In female subjects, the activation of Panx1 led to the release of leptin, a hormone previously linked to heightened pain sensitivity. This finding aligns with earlier human studies from the 1980s that observed higher leptin levels in women with chronic pain.
“Injury to a nerve can be debilitating,” says Trang. “We know that a lot of preclinical research has been on male subjects. Consequently, treatments were often developed from a male-based understanding and may not be very effective in females.”
The 2019 Canadian Pain Task Force report highlighted the disparity in chronic pain prevalence between genders, with women experiencing higher rates across all age groups. This new research offers a potential biological basis for this observation.
Dr. Lori Montgomery, MD, a pain clinician and clinical associate professor at the CSM, emphasized the clinical significance of these findings. “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,” she stated. “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.”
The study’s first authors are Churmy Y. Fan, Ph.D., Brendan B. McAllister, Ph.D., and Sierra Stokes-Heck.
The research was published in Neuron, DOI: 10.1016/j.neuron.2025.01.005.
Disclaimer: This article is based on a study conducted on rodents and may not directly translate to human physiology. While the findings offer valuable insights into potential sex-specific differences in pain pathways, further research is necessary to validate these results in human subjects and to develop targeted pain management strategies. This article is for informational purposes only and does not constitute medical advice. Consult with a healthcare professional for any concerns regarding pain management.
