Summary: We know women are more likely to report chronic pain. But why women are more sensitive to pain is poorly understood. A new study shows that male and female pain receptors differ a lot. Female receptors react more to prolactin. Male receptors react more to orexin B.
Some things are well known but poorly understood. One is that women are more likely to have chronic pain. They are also more likely to be diagnosed with conditions tied to chronic pain. So women are more likely to get problems like irritable bowel syndrome, fibromyalgia, and other chronic pain conditions.
People often assume these differences come just from sex hormones. That may be partly right. But researchers now think there is more to the story. A new study suggests pain receptors may differ a lot between men and women. Many factors may cause this. This new theory may completely change the approach to managing pain in males and females.
Do men and women feel pain differently?
One of the latest studies looked at how pain receptors in the body become more sensitive (peripheral nociceptor sensitization), and how this differs between the sexes. Nociceptors are the nerve cells that detect painful triggers. Under certain conditions they become more sensitive, which lowers the point where you feel pain. This is a key factor in many pain conditions. But until now, no one had closely studied whether it happens differently in men and women.
To find out, researchers used a lab method called patch-clamp electrophysiology. It measured how easily dorsal root ganglion (DRG) nerve cells fire. These cells came from male and female rodents, monkeys, and humans. The study focused on prolactin and orexin B, two natural compounds (hormones) known to affect pain. Earlier studies showed prolactin boosts pain responses only in female rodents. This study confirmed it. Prolactin made DRG nerve cells more sensitive in female mice but not male mice. The same female-only effect showed up in female macaque monkeys and human female DRG nerve cells. So the effect holds across species. Since prolactin is more abundant in females, females are more sensitive to certain pains.
The study also found that orexin B (more abundant in males) sensitized DRG neurons in male but not female mice, macaque monkeys, and humans. This male-only effect was tied to more orexin receptor 2 in male DRG nerve cells. Female nerve cells had more prolactin receptors instead. Tissue staining backed this up. It showed more of each receptor matching the trigger in each sex.
These results reveal a basic difference between the sexes in how pain receptors become sensitive. This is one of the first studies to show that men and women feel pain through different mechanisms.
This finding matters a lot for pain care. Today, a patient’s sex is not usually considered when choosing pain treatments. But this study suggests that tailoring treatment to the patient’s sex could greatly improve results. For instance, targeting prolactin pathways might be more effective in treating pain in women, while targeting orexin pathways could be more beneficial for men.
The study also shows that pain drug trials need to account for sex. Trials should include balanced numbers of men and women and look at results by sex. Then researchers can better see how well treatments work. They may also find out why past trials failed. Looking back at past trials with this in mind may give useful insights and lead to better pain treatments built for each sex.
What does this mean for pain treatment in men and women?
This study gives strong evidence that pain receptors become sensitive differently in men and women. The difference shows up in many species, including humans. In women, prolactin plays a big role in making pain receptors sensitive. In men, orexin B does. The study also shows why a patient’s sex should be part of pain care. The findings support a more personal approach to pain therapy. Treatments should fit the different biology of male and female patients.
Frequently asked questions
Who can endure more pain, male or female?
This study did not measure pain tolerance. But it helps explain why women report more pain. Female pain nerves became more sensitive when exposed to prolactin, a hormone more abundant in females. A sensitized nerve fires more easily. Male pain nerves responded to orexin B instead. The difference is less about toughness and more about how each sex’s pain receptors are wired.
Why do women get more chronic pain than men?
Women are more likely to report chronic pain and to be diagnosed with painful conditions such as irritable bowel syndrome and fibromyalgia. Sex hormones explain part of it. This study adds another piece. Female pain receptors carry more prolactin receptors, and prolactin makes them more sensitive. So certain pains register more strongly in women.
What are prolactin and orexin B, and how do they affect pain?
Prolactin and orexin B are two natural compounds in the body that affect how pain is felt. In the study, prolactin made pain nerves more sensitive in females but not males, in mice, macaque monkeys and humans. Orexin B did the reverse. It made male pain nerves more sensitive, and those nerves carry more orexin receptor 2. That split points toward treatments aimed at prolactin pathways for women and orexin pathways for men.
Source:
Stratton, H., Lee, G., Dolatyari, M., Ghetti, A., Cotta, T., Mitchell, S., Yue, X., Ibrahim, M., Dumaire, N., Salih, L., Moutal, A., François-Moutal, L., Martin, L., Navratilova, E., & Porreca, F. (2024). Nociceptors are functionally male or female: From mouse to monkey to man. Brain, awae179. https://doi.org/10.1093/brain/awae179
Dr. Gurpreet Singh Padda, MD, MBA, MHP
