Biology may be painful destiny

The source of Beth Hoffman's pain remains as elusive as the cure she so desperately seeks. The discomfort in her jaw started when she was 21, the year her wisdom teeth were removed and she gave birth to her first child.

Now 29, she still suffers constant headaches and neck spasms. At night, her jaw feels as though it is being held closed by a rubber band, preventing her from talking with her family.


"It's hard to figure out exactly why it happened or how to fix it," said Hoffman, who lives near Patterson Park in Baltimore.

One possible explanation for the mysterious pain is her gender.


Evidence has been building in recent years that women are more sensitive to pain than men and that underlying biological differences between the sexes are at least partly responsible. Some experts think hormones play a role, because women's pain sensitivity seems to fluctuate with their estrogen levels.

Gender-specific wiring of the nervous system also might be involved. Neurological circuits that process pain signals were once seen as resembling phone lines running from body to brain. They now appear to be complex networks, and somewhere along the evolutionary line, men and women might have signed up for different calling plans.

Discovering what makes women more sensitive to pain could lead to gender-specific therapies, scientists say. It might also help explain why far more women develop chronic pain disorders.

"For a long time, pain sensitivity was seen as a psychological problem, but now people are looking at it as a pain-processing problem," said Joel Greenspan, a pain researcher at the University of Maryland Dental School.

Until the mid-1990s, most scientists ignored gender as a factor in pain sensation, and early studies of the subject were often an afterthought.

"They'd realize they had data on men and women and go fishing for evidence of some difference," Greenspan said.

In 1995, a group of scientists surveyed the published research and found that two-thirds of the studies concluded that women were more sensitive to pain than men were.

"Nobody was reporting the opposite, that men were more sensitive," Greenspan said. "That started a lot of us asking if there's some explanation."


The notion that women are more prone to pain disorders with no clear cause also aroused scientific curiosity. Women with fibromyalgia, which produces pain over large areas of the body, outnumber men with the condition by 9-to-1. Irritable bowel syndrome, the symptoms of which include abdominal pain or cramping, is also more common among women.

Gender roles defined by culture could partly explain the gap. For example, experts note that women more readily admit feeling pain than men do and tend to seek medical care more often.

One study found that men reported less pain if a female technician conducted the experiment, highlighting the link between machismo and stoicism.

"It could partly be social reasons, that women are permitted to express pain," said Lynda LeReche, a clinical pain researcher at the University of Washington.

In the past, women's complaints about mysterious pains were attributed to an overactive female imagination. "It was dismissed as some kind of hysterical syndrome," Greenspan said.

Scientific evidence suggests the heightened discomfort is because of the way a woman's brain or other portion of her nervous system processes pain. Research has provided a few clues.


In a 2003 brain scan study at the University of California, Los Angeles, volunteers responded differently to pain based on their gender.

Women's emotional centers were more active during pain, while men's analytical regions handled the bulk of the pain processing. One possible explanation is that the differences stem from primitive times, when men's role was to fight to defend the clan, and women's role was to protect and nurture children.

Estrogen, a sex hormone tied to women's reproductive physiology, has also emerged as a contributor to pain differences.

"We are really zeroing in on hormonal changes," said Dr. Edward G. Grace, a specialist in temporomandibular joint pain at the UM Dental School, who has been treating Beth Hoffman for the past year. "If I had to bet on anything to explain it, I'd bet on estrogen."

In recent years, scientists have found that many human cells respond to estrogen, including the nerves that carry pain signals. Also, female pain sensitivity seems to vary depending on estrogen levels in the body.

TMD, a common set of painful, chronic conditions involving muscles, nerves and joints in the jaw, neck and head, has been one focus of pain research.


LeReche had a group of women with TMD keep journals of the pain they felt during their menstrual cycles. The women experienced more pain during menstruation and ovulation, times when estrogen levels fluctuated.

Age-related hormonal changes also seem to alter pain perception. Women are at greater risk for chronic pain during their childbearing years and report less pain before puberty and after menopause.

LeReche speculates that estrogen takes over a woman's pain-sensing system during her reproductive years, possibly to help blunt the trauma of childbirth.

"During pregnancy, estrogen goes way up," she said. "It may be that it evolved to help women during labor."

The Maryland researchers have unearthed another possible explanation for the pain gap, a difference in wiring that allows the female nervous system to become overly sensitive.

In their Baltimore laboratory, they constructed a pain-inducing machine that poked people's fingers with a metal rod. Volunteers gamely inserted their hands into the device to receive a fast series of jabs, just hard enough to hurt. The machine applied the same amount of force each time.


Male volunteers felt no change in the amount of pain with each subsequent jab, but female volunteers said it got worse. Because the force of the poking didn't change, the researchers concluded that the women must have become more sensitive as the jabbing continued.

Spinal nerves acting as a switchboard between the body's pain sensors and the brain probably play a key part in the process, Greenspan said.

With the onset of poking, skin sensors send a whisper of a pain signal to the spinal nerves, which relay the message to the brain. If the poking continues, the spinal nerves amplify the signal, so instead of a whisper, the brain hears a scream.

Women with TMD, they found, generally feel more pain than do men with TMD or healthy people of either sex.

"There seems to be some kind of global change," Greenspan said. "The entire pain-processing system in women with TMD is altered."

That might explain why more women get TMD pain in the first place and why women are more likely to develop other chronic pain disorders.


Researchers hypothesize that a previous painful experience - or some incident in everyday life - might hypersensitize some women, making them more likely to perceive pain from conditions such as TMD, irritable bowel syndrome and fibromyalgia.

Greenspan said doctors might one day consider hormones and other gender differences when treating women for pain. Studies in rats have shown that morphine's effectiveness in reducing pain in females varies with their estrogen level.

"Maybe we could give doctors a way to modulate the estrogen so the opiates work better," Greenspan said.

Preventing such hypersensitivity, he said, might prevent chronic pain from developing.

"You're not just dealing with the inciting pain problems; you're dealing with the change in the nervous system," he said.

Whatever change left her in pain - whether it was related to her wisdom teeth, having her first child or both - Beth Hoffman has suffered ever since.


Now pregnant with her second child, she has stopped taking a daily dose of ibuprofen to blunt her headaches.

"It's tough," she said. "I could chew a piece of gum and be in serious pain for a couple of days. Then I just kick myself for not being more disciplined."

Over the past year, with help from UM dentists, she has tried a number of new pain-relief therapies such as using heating and cooling pads, avoiding chewy foods and trying to avoid stress. The therapies have helped, she said, but the problem remains.

Echoing research findings, she has noticed that her pain seems to fluctuate with her monthly cycle, peaking during menstruation. She has heard that TMD pain sometimes subsides in women who are carrying a child. She hopes that will prove true with her current pregnancy.

She also wonders whether the problem originated with her first pregnancy.

"I think the dental surgery originally aggravated it," she said, "but it very well could have been the hormonal changes I went through. It was also the beginning of parenthood and high levels of stress."