Why Women Are Living in the Discomfort Zone
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.
显然，我被拉进了越来越庞大的生活在慢性疼痛中的美国成年人的队伍。根据美国医学研究所(Institute of Medicine)的数据，我发现像我们这样的人有一亿之多。这是最让我吃惊的事情，其次就是当中的多数人为女性。没有人真正了解原因。
明确的一点是，女性与男性对疼痛及止痛药的反应非常不同。加拿大麦吉尔大学(McGill University)研究疼痛问题的遗传学家杰弗里·莫吉尔(Jeffrey Mogil)就半开玩笑地说道，某一天我们或许会给女性开粉色药片，给男性开蓝色药片。
在2009年的一项研究综述中，佛罗里达大学(University of Florida)的研究人员发现，从全世界范围来看，女性患肠激惹综合征、纤维肌痛、头痛（尤其是偏头痛）、神经病理性疼痛（因神经系统本身受创造成）、骨关节炎、如颞下颌关节紊乱症(TMD)之类的下颌病症、肌肉骨骼疾病以及背痛的比例更高。在2012年的一项大型研究（该类研究中规模最大）中，斯坦福大学(Stanford University)的研究人员证实了这一发现。
乔治城大学(Georgetown University)的研究人员在1999年实施了一个巧妙的实验。他们拍下了伪装成胸痛病人的专业演员，然后把录像展示给700名全科医生并给他们提供了每位假冒患者的信息。结果是，医生不大相信胸痛的女性患有心脏病。同样地，欧洲研究者查阅了3,779名心脏病患者（42%为女性）的病例，发现女患者受到的治疗不如男患者周全。梅约医院(Mayo Clinic)在2000年对2,271名因胸痛去往急诊室的男女患者的调查发现了同样的结果。
前奥运赛艇选手、目前于佛罗里达杰克逊维尔市(Jacksonville)梅约医院矫形科担任主任的玛丽·I.·奥康纳(Mary I. O'Connor)称，女性获得所需的髋关节或膝关节置换手术的几率比男性低两倍。即使她们最终做上了手术，效果也往往不如男性好，这一问题被她称为“永远追不上综合症”。
以果蝇的情况为例，北卡罗来纳州立大学(North Carolina State University)的研究人员指出雄果蝇与雌果蝇有多达90%的基因的表达模式不同。换句话说，就果蝇基因组的几乎所有基因而言，性别在决定某个基因的活跃程度──即它有多“兴奋”以及它在果蝇的生理与行为方面发挥多大作用──上扮演着重要角色。探索基因表达模式中的此类性别差异有助于研究人员了解疼痛处理与性别有关的差异。
很明显，在年龄较小时，男孩与女孩表现出的疼痛模式大致相似，直到青春期为止。一旦到了青春期，某些类型的疼痛在女孩当中就明显变得更常见。即使某类疼痛病症在男孩与女孩中的发病率相同，女孩的疼痛剧烈度也往往比男孩强。这一情况在偏头痛问题上尤为明显。在青春期前，男孩与女孩的患病率基本相同。在青春期后，女性的发病率变成18%，而男性的比例只有6%或7%。华盛顿大学(University of Washington)的研究人员指出，颞下颌关节病(TMJ，现称为TMD)的模式也类似。
此外，还存在“疼痛灾难化”的问题。通常说来，研究显示女性比男性更倾向于把事情想得很糟糕，即想象最糟糕的状况并认为疼痛不会休止。这种做最坏打算的倾向甚至在名为“功能性核磁共振成像(fMRIs)”的脑部扫描中也体现出来。比如说，在多伦多大学(University of Toronto)的一项研究中，研究人员展示尽管做最坏打算并未影响大脑处理实验性疼痛的感觉方式，但它确实让大脑的情绪区出现活动。
加州大学洛杉矶分校(University of California, Los Angeles)儿科麻醉师朗尼·泽尔策(Lonnie Zeltzer)指出，”疼痛灾难化”实际上可能是个后天习得的行为；女孩似乎比男孩更容易从母亲那里习得以语言或非语言形式表现的对疼痛的灾难化。。好消息是研究显示认知行为疗法可减轻这种倾向。