Study Explains Pain Differences in Men and Women

Researchers have finally discovered what makes men and women experience pain differently.

Increasing research suggests that males and females differ in their experience of pain. While women are generally thought to have a higher pain threshold because they have evolved to be able to cope with the pain of childbirth, studies suggest men may have higher pain thresholds and tolerance.

Moreover, different sexes seem to respond to pharmacological and non-pharmacological pain interventions differently.


A new study published in the journal BRAIN is the first to explain the mechanisms behind the differences in pain perception.

Researchers at the University of Arizona Health focused on the excitability of nociceptors, the specialized nerve cells that produce pain and are located near the spinal cord.

When activated by damage or injury, nociceptors send a signal through the spinal cord to the brain, resulting in pain perception. Nociceptors are also adaptable in their response to injury.

When a person is injured, pain medications, including nonsteroidal anti-inflammatory drugs like ibuprofen and aspirin, work by normalizing the threshold for nociceptor activation, thereby blocking pain produced by low-intensity stimuli.

In the study, researchers chose two substances, prolactin and orexin B. Prolactin is a hormone responsible for lactation and breast tissue development, while orexin is a neurotransmitter that promotes wakefulness. However, both substances have many other functions that are only now being discovered.

The researchers used tissue samples from male and female mice, nonhuman primates, and humans to test the effect of prolactin and orexin B on nociceptor activation thresholds that can allow low-intensity stimuli to produce pain.

They found that different things change the thresholds of nociceptors in males and females in both animals and humans.

"When we added the sensitizing substances that lower these thresholds for activation, we found that prolactin only sensitizes female cells and not male cells, and orexin B only sensitizes male cells and not female cells. The startling conclusion from these studies is that there are male nociceptors and female nociceptors, something that has never previously been recognized," said Frank Porreca, Ph.D., research director of the Comprehensive Center for Pain and Addiction at The University of Arizona Health Sciences.

Blocking prolactin signaling reduced nociceptor activation in females and had no effect in males, while blocking orexin B signaling was effective in males and not in females.

Researchers say their findings emphasize the importance of a precision medicine-based approach that considers patient sex as fundamental when choosing treatments for pain management.

Many pain conditions, such as migraine and fibromyalgia, are much more prevalent among women than men. They could be potentially treated by preventing prolactin-induced nociceptor sensitization.

In men, targeting orexin B-induced sensitization might improve the treatment of pain conditions associated with nociceptor activation.

Pain in men versus women

Research in pain perception may be complicated, as studies often rely on participants self-reporting their experiences. Sociocultural and psychological influences can also play a role.

For example, men learn at a young age to be "tough," which may lead them to not "complain" about pain. In a 1991 experiment, men exposed to cold presser pain reported significantly less pain in front of a female experimenter than a male experimenter.

At the same time, women's pain is often seen as exaggerated. According to a 2019 survey, one in four women with chronic diseases said a healthcare provider did not take their pain seriously.

Even some scientific literature defines pain as "a natural characteristic of women's bodies," while women in pain can be perceived as hysterical or emotional.

A better understanding of differences in the experience of pain can improve treatments for chronic pain conditions.



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