Why Chronic Pain May Differ Between Women and Men

New Research Identifies Sex-Specific Mechanisms Behind Chronic Pain

A new study from the University of Calgary provides insight into why women are more likely to experience chronic pain than men. The research, led by Dr. Tuan Trang, Ph.D., highlights biological differences in how pain is processed between sexes, which may influence treatment responses. Published in Neuron, the study builds on previous findings that chronic pain is more prevalent among women and identifies a potential hormonal factor contributing to pain sensitivity.

Leptin’s Role in Heightened Pain Sensitivity

The study, conducted in rodents, focused on neuropathic pain—pain caused by nerve damage, which can lead to allodynia, where normally non-painful stimuli become painful. Researchers found that while both male and female rodents process pain through pannexin 1 (Panx1) channels, they do so via different immune cells. In female rodents, activation of these channels leads to the release of leptin, a hormone associated with increased pain sensitivity.

These findings suggest that biological sex differences could play a key role in how chronic pain develops. While previous research has shown that women with chronic pain tend to have higher leptin levels, this study provides new insights into how the hormone is involved in pain signaling.

Implications for Personalized Pain Treatment

Dr. Lori Montgomery, MD, a pain clinician and clinical associate professor at the University of Calgary, emphasized the need for more research into sex and gender differences in pain management. “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,” she noted.

Because much preclinical pain research has historically been conducted in male subjects, treatments have often been developed from a male-based understanding of pain. This study highlights the importance of considering sex-specific biological processes when developing pain management strategies. Further research is needed to determine how these findings could be applied in clinical settings, but they underscore the potential for more tailored, effective treatments for chronic pain in women.

Source:

Fan, Churmy Y., Brendan B. McAllister, Sierra Stokes-Heck, Erika K. Harding, Aliny Pereira de Vasconcelos, Laura K. Mah, Lucas V. Lima, et al. 2025. “Divergent Sex-Specific Pannexin-1 Mechanisms in Microglia and T Cells Underlie Neuropathic Pain.” Neuron, January. https://doi.org/10.1016/j.neuron.2025.01.005.