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Why do females feel more pain than males do? Add to ...

The pain starts after a trivial injury, a scraped knee or even a paper cut, but endures or intensifies long after the original wound has healed.

Even a light breeze or the touch of a bed sheet can be unbearable for patients with the rare disorder known as complex regional pain syndrome, which affects far more girls than boys, and significantly more women than men.

No one knows why, says Steve Brown, a doctor who treats chronic pain at the Hospital for Sick Children in Toronto. He sees seven or eight girls with the disorder for every boy with it.

"I don't think anyone has a good answer."

The question is part of a larger mystery, one that intrigues researchers as they work toward a more profound understanding of the biology of pain. Why is it that females feel pain more than males?

Study after study -- most of them done in adults -- show this is the case. Women yank their arms out of icy or hot water faster than men, or report significantly higher levels of pain than men from the same mild electric shock. The difference isn't huge, but it is significant.

This might come as a surprise to many women, especially those who have been through labour.

But scientists have moved beyond documenting the phenomenon to explaining it. They are now zeroing in on different genes, pain mechanisms and pathways in women and men, and on the role that sex hormones play.

One day, they hope to be able to tailor pain relief for men and women - blue pills and pink pills. Their work could lead to new treatments for chronic pain conditions, such as complex regional pain syndrome, that affect more women then men. In adults, the literature suggests two women get it for every man.

It is unclear how early the differences begin. There are studies that suggest girls are more sensitive to pain than boys are, although the research is not as conclusive as in adults, says Patricia McGrath at the Hospital for Sick Children. She and Dr. Brown are part of research project studying a number of chronic pain conditions -- including complex regional pain syndrome and headaches -- that seem to affect girls more than boys.

By adulthood, experts say, almost every chronic pain condition is more prevalent in women than in men.

Hormones are part of the explanation, says Serge Marchand, a researcher at the University of Sherbrooke. Female rats have more intense reactions than males to the same painful stimulus, like an electric shock. But if you remove their ovaries and testes, so that they don't produce sex hormones, then males and females respond the same way.

Why?

Dr. Marchard thinks hormones might affect the body's built-in ability to mute pain. Both mice and humans have systems that regulate pain, natural opioids, cannaboids and other neurotransmitters. They allow people to function despite injury or illness.

He asked female volunteers to come to his lab three times in a single month, so he could test the effectiveness of their natural pain-killing systems at different times in their menstrual cycle.

First, he administered a mild electrical shock on their left legs, and asked them to rate the pain on a scale of one to 100. Then he asked them to put their right arms into water chilled to five degrees Celsius.

The cold triggered natural pain control. Previous experiments have shown that when volunteers are then shocked a second time, they report significantly less pain. The body's response to their freezing arm makes their leg less sensitive to being zapped.

But as Dr. Marchard discovered, and reported at a conference in Oregon earlier this year, there were big difference in natural pain control, depending on where a woman was in her monthly cycle.

When women were ovulating, and had high levels of estrogen, they reported as much as 70 per cent less pain after the second shock. But if they were menstruating, and had low levels of estrogen, they reported as little as 30 per cent less pain.

Men, however, don't have these kinds of ups downs in pain modulation, although there is evidence that testosterone, a male hormone, plays a role in pain tolerance.

Hormones, however, are only part of the pain picture. Our genes might also explain why women feel pain more than men do.

A number of researchers have found evidence that men and women control pain in different ways. Male mice, they have discovered, have a natural pain-control system that females don't have. The key to the system is a protein called GIRK2, which plays a role in communication between cells.

Jeffrey Mogil, at McGill University in Montreal, has found that a gene that causes red hair and fair skin also plays a role in how some women -- but not men -- respond to painkillers.

This means the neural circuits involved in inhibiting pain are different in men and women, he says.

"The idea was pretty radical even 12 years ago. It is really starting to be believed now."

There is no big picture yet, just hints that genes involved in pain for one sex aren't important in the other.

"It is not too hard to convince yourself that there may have been separate adaptive pressures that would have led to the development of different circuits," he says.

Men would have benefited from a system that allowed them to deal with traumatic pain to the skin, whereas women would have benefited more from a system that helped them endure more visceral pain, like childbirth.

It is fun to speculate, says Dr. Mogil, but these kinds of theories are impossible to prove.

Dr. Marchand has come up with one to explain why women would have evolved to have the most natural pain control when they are ovulating, which is not painful, and the least when they are menstruating, which can involve pain.

It seems unfair. But for many animals, he says, sex is painful. So it makes sense to have a system that provides maximum pain control when intercourse is most likely. "Otherwise they would never have offspring."

Maybe we inherited this system, he says.

TOMORROW: Hurdles to getting help

 

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