Here is finally why men and women perceive pain differently

The differences in pain perception between sexes are linked to nociceptors, specialized nerve cells, according to a recent study from the University of Arizona, published in Brain. Researchers identified for the first time functional differences between male and female nociceptors, paving the way for precision medicine that takes the patient's sex into account for pain treatment.


Research on mice and monkeys, led by Frank Porreca, research director at the Comprehensive Center for Pain & Addiction at the University of Arizona, demonstrated that nociceptors, the nerve cells responsible for pain perception, are different in males and females. This discovery could lead to the development of more effective treatments to manage pain in men and women differently.

The team focused on the excitability of nociceptors located near the spinal cord, in the dorsal root ganglion. These cells, when activated by injury or damage, send a signal to the brain via the spinal cord, resulting in the perception of pain. Nociceptors can adapt to injuries, for example by increasing their sensitivity after a sunburn, making normally harmless stimuli painful.

To understand these differences, the researchers tested the effect of prolactin and orexin B on the activation thresholds of nociceptors. Prolactin is a hormone involved in lactation, while orexin B is a neurotransmitter that promotes wakefulness. They used tissue samples from male and female mice, non-human primates, and humans. The results showed that prolactin sensitizes only female nociceptors, whereas orexin B sensitizes only male nociceptors.

These findings indicate that the underlying mechanisms of pain are different between sexes. By blocking prolactin signaling, the researchers reduced nociceptor activation in females, with no effect in males. Conversely, blocking orexin B decreased nociceptor activation in males, with no impact on females.

These results suggest that pain treatments could be improved by specifically targeting the mechanisms unique to each sex. For instance, pain disorders more common in women, such as migraines and fibromyalgia, could benefit from treatments that prevent prolactin-induced sensitization. Similarly, targeting orexin B could improve pain management in men.

Frank Porreca and his team plan to continue their research to identify other sexually dimorphic pain mechanisms. They hope these efforts will lead to the development of more precise and effective treatments for men and women by integrating the sexual dimension right from the conception of pain therapies.