Sunday, February 9, 2014

In my practice, I listen to complaints of pain all day long...and most of my patients are women...and their pain is real. There are a lot of reasons why women have chronic pain but all to sadly, their complaints are too often ignored by their healthcare provider. In a Wall Street Journal article, an author details the clinical and socio-psychological aspects of pain and how she came to find the right doctor who listened.


The Saturday Essay

Why Women Are Living in the Discomfort Zone

More than 100 million American adults live with chronic pain—most of them women. What will it take to bring them relief?


By

Several years ago, my neck suddenly went bonkers—bone spurs and a long-lurking arthritic problem probably exacerbated by too many hours spent hunching over a new laptop. On a subjective scale of zero to 10 (unfortunately, there is no simple objective test for pain), even the slightest wrong move—turning my head too fast or picking up a pen from the floor—would send my pain zooming from a zero to a gasping 10. 

Sitting in a restaurant was agony if the table was too high; it forced my arms and shoulders up. So was sitting in the movies, looking up to see the screen. Shifting from sitting to lying down in bed was excruciating; there is simply no way to do it with a bad neck. Even stupid little things like bending forward to paint my toenails became impossible. 

I had been inducted, apparently, into the growing army of American adults living in chronic pain. I discovered that there are 100 million of us, according to the Institute of Medicine. That was surprise No. 1. Surprise No. 2 was that most of us are women. Nobody really knows why. 

There are cultural factors, to be sure. Women are "allowed" to be emotional about their pain, and men often aren't, so perhaps women's pain gets noticed more. There are complicated hormonal factors too. There are research biases at work as well, including the absurd fact that most basic neuroscience work on pain pathways is done not only in rats but in male rats. Go figure.

What is clear is that women and men can react so differently to both pain and pain medications that, as the McGill University pain geneticist Jeffrey Mogil only half-jokingly puts it, we may someday have pink pills for women and blue pills for men. 

Here's what we do know. Clinically, women are both more likely to get chronic painful conditions that can afflict either sex and to report greater pain than men with the same condition, according to studies over the past 15 years. (Women also have more acute pain than men even after the same surgeries, such as wisdom tooth extraction, gall bladder removal, hernia repair and hip and knee surgery.)

In 2008, when researchers looked at prevalence rates in 10 developed and seven developing countries, in a sample that included more than 85,000 people, they discovered that the prevalence of any chronic pain condition was 45% among women, versus 31% among men.

In a 2009 review, researchers from the University of Florida found that, all over the world, women get more irritable bowel syndrome, more fibromyalgia, more headaches (especially migraines), more neuropathic pain (from damage to the nervous system itself), more osteoarthritis and more jaw problems such as TMD, as well as more musculoskeletal and back pain. In a large 2012 study (the biggest of its kind), Stanford University researchers confirmed this picture. 

And it isn't just clinical pain conditions that reveal an unequal burden of suffering. Sex differences have also shown up in lab experiments in which people voluntarily let scientists test their responses to pain stimuli, though recent research suggests that these differences are more complicated than once thought.

Historically, women have repeatedly been shown to be more sensitive to experimental pain stimuli than men—with lower pain thresholds (that is, they report pain at lower levels of stimulus intensity) and lower tolerance (they can't bear intense painful stimulation as long). More recent work shows that the type of pain stimulus—heat, cold, mechanical pressure, electrical stimulation, ischemic pain (from tourniquets cutting off blood supply) and other methods—matters a lot in the attempt to tease out gender differences. 

In a recent systematic review of 10 years' worth of data from pain labs, Canadian researchers found that men and women have comparable thresholds for cold and ischemic pain but that women have lower pain thresholds for pressure-induced pain than men. It's unclear why. With tolerance, there is strong evidence, the team found, that women tolerate less heat and cold pain than men, but that tolerance for ischemic pain is comparable in men and women. Again, it isn't clear why.

The more pressing question, of course, for millions of women in chronic pain is how well their pain will be managed once they seek help.

A few studies suggest that when women in chronic pain seek care in emergency rooms, they are offered comparable doses of opioids ("narcotics") as men and sometimes are actually offered more aggressive treatment. Chronic pain, by the way, isn't just acute pain that doesn't go away after a few months; it's a transformation of the nervous system that can literally shrink the brain.

But many other studies point to undertreatment of women's chronic pain—a pattern that fits an overall picture of differential care for men and women. With heart attacks, for instance, a team of Canadian researchers reviewed the charts of 142 men and 81 women with comparable symptoms and reported in 2002 that men were more likely to be given lipid-lowering drugs, to get angiograms (to detect potentially clogged blood vessels) and to have coronary-artery bypass surgery. 

Other data suggest that women are also less likely than men to be admitted to intensive care units and to get certain procedures, such as being put on a respirator, once they arrive there; they are also more likely to die in the ICU, in the hospital or within a year of admission. A 2007 Rhode Island study looked at 30 men and 30 women who had just had coronary-artery bypass surgery and tracked the medications they were given. The researchers were astonished to find that men got pain medications, while women got sedatives.

With chronic pain problems, women's symptoms are often minimized.

In a clever 1999 study, researchers from Georgetown University videotaped professional actors portraying people with chest pain. The researchers showed the videos to more than 700 primary care physicians and gave them data about each hypothetical patient. The doctors were much less likely to believe that the women with chest pain had heart disease. Similarly, when European researchers looked at the records of 3,779 heart patients, 42% of them women, they found that women weren't worked up as thoroughly. It was the same story in a 2000 Mayo Clinic of 2,271 men and women who went to the emergency room with chest pain. 

To be sure, chest pain and heart attacks can be especially tricky to diagnose because women and men tend to exhibit somewhat different symptoms. But less complicated medical problems, such as the knee pain of osteoarthritis, exhibit the same pattern of differential treatment.

Women are three times less likely to get the hip or knee replacement they need, according to Mary I. O'Connor, a former Olympic rower who now heads the orthopedic surgery department at the Mayo Clinic in Jacksonville, Fla. And when they do finally have the surgery, they often don't do as well as men, a problem she calls the "never-catch-up syndrome." 

Part of the problem is that women usually wait longer to have surgery, Dr. O'Connor has found, in contrast to men, who tend to seek surgery before their pain becomes extreme. The surgery itself is equally beneficial for both sexes, but because a woman typically has more advanced disease by the time she gets surgery, the result often isn't as good. 

Another factor may also be at work here: an unconscious bias that can make doctors less likely to recommend surgery to a woman with moderate knee arthritis. 

In a 2008 study, Canadian researchers looked into this very question, asking 38 family physicians and 33 orthopedic surgeons to evaluate one "standardized," or typical, male patient and one "standardized" female patient with moderate knee arthritis. ("Moderate" means a degree of arthritis in which it's a judgment call whether surgery is necessary or not.) 

The odds of a surgeon recommending knee replacement were 22 times higher for the male patient than the female, the Canadian team found. 

Women are under-treated for abdominal pain, too, a 2008 study showed. In Philadelphia, emergency room doctors kept track of 981 men and women who arrived with acute abdominal pain. The men and women had similar pain scores, but women were significantly less likely to get any kind of pain medication and were 15% to 23% less likely than men to get opioids specifically. Women also had to wait longer before they got any pain medicine—65 minutes on average, compared with 49 for men. Cancer and AIDS patients have displayed the same pattern, with women much less likely than men to get adequate pain treatment.

And consider this: In Sweden, researchers used a modified version of a national exam for young doctors in which hypothetical patients with neck pain were described. Some of the hypothetical patients were male and some female; all were described as bus drivers who were living in tense family situations. The interns taking the exam were more likely to ask female patients psychosocial questions (implying a psychosomatic origin of the pain) and more likely to request lab tests in the males. Female interns were just as biased as males. 

So if women have more chronic pain than men—and they do—the obvious question becomes: Why?
At the most basic biological level—the expression (activation) of genes, including genes that control responses to pain stimulation—gender has a very significant effect. 

In fruit flies, for instance, researchers from North Carolina State University have shown that males and females are different in the expression of a whopping 90% of all their genes. In other words, for almost all the genes in the fly's genome, sex plays a significant role in how active a particular gene is—that is, how much it is "turned on" and how much of a role it plays in the animal's physiology and behavior. Exploring such sex differences in gene expression could help researchers understand sex-related differences in pain processing. 

Sex hormones also play a major role in the different ways men and women experience pain, though the hormonal connection is proving nightmarishly tricky to unravel. 

It's clear that, as young children, boys and girls show comparable patterns of pain—until puberty. Once puberty hits, certain types of pain are strikingly more common in girls. Even when the prevalence of a pain problem is the same in both sexes, pain severity is often more intense in girls than boys. That is especially true with migraines. Before puberty, boys and girls get roughly the same number. After puberty, the prevalence becomes 18% for women and 6% or 7% for men. A similar pattern holds for TMJ, temporomandibular joint disease (now called TMD), as University of Washington researchers have shown. 

Overall, many researchers think that testosterone generally protects against pain, an idea shown in some rat studies. If newborn male rats are castrated, they are unable to produce testosterone later, during puberty. The result? The animals become less sensitive to the pain-reducing effects of the opioid, morphine, and thus more susceptible to pain. If newborn female rats are given testosterone, they get better pain relief from morphine. (A word of caution, though: It isn't clear how well pain findings in rats translate to people.)

But if the role of testosterone in pain is relatively straightforward (more testosterone, less pain), the role of estrogen is anything but. 

Genetics research suggests that estrogen reduces the activity of one of the leading "pain genes," called COMT. The job of the COMT gene is to get rid of stress hormones such as epinephrine. That means that if COMT activity is too low, the body can't get rid of stress hormones as well. And since stress hormones act directly on nerves to rev up pain, the net result of estrogen acting on COMT is more pain, according to researchers at the University of North Carolina.

Other research, too, supports the "estrogen is bad " pain theory. Consider what happens when transsexuals take hormones to enhance the sexual characteristics of their new sex. In one preliminary study, Italian researchers tracked male-to-female human transsexuals, who must take estrogen to enhance female sex characteristics. They found that approximately one-third develop chronic pain, especially headaches. The researchers also looked at female-to-male transsexuals, who must take testosterone to enhance male characteristics; their chronic pain went down. 

But often, things aren't that simple. At menopause, for instance, women's ovaries stop pumping out estrogen. To combat the symptoms caused by this drop in estrogen, many women begin taking exogenous estrogen—that is, estrogen not made naturally in the body but taken as a drug. If the general theory—that estrogen increases pain—is true, you would expect that taking exogenous estrogen (hormone-replacement therapy) would make pain worse. But in truth, sometimes exogenous estrogen makes pain worse, sometimes it doesn't, and sometimes it makes it better. 

And then there is the "catastrophizing" problem. In general, studies suggest that women are more likely than men to catastrophize—that is, to imagine worst-case scenarios and to believe that the pain will be unending. The tendency to catastrophize even shows up on brain scans called fMRIs. In one University of Toronto study, for instance, researchers showed that while catastrophizing didn't affect how the brain processed the sensory aspect of experimental pain, it did make the emotional regions of the brain light up. 

Catastrophizing may actually be a learned behavior; girls, more than boys, seem to pick up verbal and nonverbal catastrophizing cues about pain from their mothers, says Lonnie Zeltzer, a pediatric anesthesiologist at University of California, Los Angeles. The good news here is that studies show that cognitive behavioral therapy can help reduce the tendency to catastrophize.

Where does all this leave women in pain?

To some extent, in the same boat as men in pain. Both men and women often have to be extremely persistent in the search for a physician who can help with their suffering. That is because most doctors don't get enough basic education about pain in medical school—a sad but well-documented fact.
But women, I believe, have to be extra-persistent, particularly if they feel their pain is being dismissed as emotional.

I know, because this happened to me with the first physician I went to for my neck pain. When she seemed to imply that there was an emotional trigger for my pain, it felt like she was literally adding insult to injury. I left that doctor and found another—a man, as it happened—who believed me and set me on a path of treatment that ultimately worked. Thankfully, I am much better now.

This essay is adapted from Ms. Foreman's new book, "A Nation in Pain: Healing Our Biggest Health Problem," published by Oxford University Press.

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