How sex differences impact treatment efficacy for chronic pain

In a recent interview with Contemporary OB/GYN, Tuan Trang, PhD, from the University of Calgary, highlighted the historical biases in preclinical chronic pain research, which predominantly focused on male subjects.

According to Trang, researchers have not historically evaluated the biological differences between men and women regarding chronic pain. This oversight led to 2 major problems. The first was an incomplete understanding of the fundamental causes of chronic pain in both sexes, and the second was the development of treatment strategies that were primarily based on male biology. As a result, many pain management approaches were not as effective for female patients, leading to significant disparities in treatment outcomes.

One of the major consequences of this research bias is that female patients, who make up approximately 70% of individuals suffering from chronic pain, often do not respond to certain treatments in the same way as male patients. Many pain management therapies were designed without considering the unique neurobiological mechanisms present in women, leading to less effective treatment options for them. However, recent advancements in research have shed light on the fact that men and women may experience chronic pain differently because of biological and fundamental differences in pain mechanisms.

Trang emphasized the importance of this shift in research. Recognizing sex-based differences in pain mechanisms is a significant step forward, as it allows for a more comprehensive understanding of chronic pain. This recognition has also opened new possibilities for drug discovery, the identification of new therapeutic targets, and the development of biomarkers that could help create more effective and personalized treatments.

Trang also acknowledged that both the research and clinical fields have made progress in addressing these disparities. The growing awareness of sex differences in chronic pain has led to a more inclusive approach in scientific studies, which could ultimately result in better treatment options for both men and women.

This video is part 2 of a 2-part series. Click here for part 1.

Reference

Fan CY, McAllister BB, Stokes-Heck S, et al. Divergent sex-specific pannexin-1 mechanisms in microglia and T cells underlie neuropathic pain. Neuron. 2025;113(6):896-911. doi:10.1016/j.neuron.2025.01.005