Chronic pain: Understanding the roots, finding the cures

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Chronic pain: Understanding the roots, finding the cures
Photo of a woman freestyle swimming in open water

Katie Pumphrey crossing the Potomac River from Maryland to Virginia, and back again totaling 15 miles.
Image courtesy Krista Mahler

On May 31, Baltimore artist Katie Pumphrey, 26, completed a 15-mile swim in the Potomac River, as preparation for next summer’s attempt to cross the English Channel — a 21-mile, open-water affair that is legendary test for endurance athletes.

Pumphrey’s story attracted attention due to this detail: she suffers from a chronic-pain syndrome called fibromyalgia. Chronic pain is a mysterious category of ailments that includes irritable bowel syndrome, chronic fatigue and, depending on the definition, Gulf war syndrome and post-traumatic stress disorder. These hard-to-treat conditions are major causes of disability, especially among women; some sufferers are trapped in a descending spiral of pain, fatigue, drug use, fear and disability.

Usually, physical pain starts as a signal from part of the body that is damaged, inflamed, deformed or diseased, but chronic pain takes a very different path, says Daniel Clauw, a professor of anesthesiology, rheumatology and psychiatry at the University of Michigan.

Which person feels pain?

X-ray of a healthy knee (left) and arthritic knee (right).

The arthritic knee on the right has lost the cartilage that normally cushions between the bones. It certainly looks painful, but the owner of the knee on the left was the one who complained of chronic pain. Although joint, bone and skin problems are often present in chronic pain, “there are people with damage to tissues who don’t have pain, and a lot of people without damage who do have pain,” says Daniel Clauw, a pain expert.
Images courtesy Daniel Clauw

Speaking in early June at a seminar for judges sponsored by the American Association for the Advancement of Science and hosted by the Neuroscience and Public Policy Program and the Law School at the University of Wisconsin-Madison, Clauw highlighted the disconnect between physical condition and pain perception with two knee X-rays.

Clauw described a range of responses to pain. “If I brought my thumb-squishing device [used to measure pain sensitivity in the lab], some of you would say it hurts with a little bit of pressure.” On that instrument, he says, “I’m very non-sensitive. I’ve never had chronic pain and probably will not.”

Women, he noted, are about 2 bars farther to the right on the curve. “Every chronic pain condition is 1.5 to 1.75 times more common in women than men.” This, rather than damage on the periphery (meaning outside the central nervous system), explains why women have more chronic pain, he adds.

In your head, but not “all in your head”

In arguing that central nervous systems with this exaggerated processing of nerve signals are instrumental to chronic pain, Clauw is not claiming that chronic pain is “psychosomatic,” something fabricated in the brain. Sensory input, he says, often triggers and then feeds chronic pain.

Response to pain in the laboratory

histogram of pain sensitivity for the general population. Distribution follows a bell-shaped design, with the majority of the population experiencing medium sensitivity to pain, and fewer numbers on the upper and lower tails of sensitivity.

The bell-shaped curve is representative of many natural phenomena. The graph shows human responses to pain are distributed on both sides of a central tendency. “People on the right side of the curve are three or four times as likely to develop chronic pain, because the brain is more sensitive,” says Clauw. “Your position on the pain curve can tell me how long you can sit in a chair before you have to move around.”
Adapted from Clauw

Like Clauw, Daniel Muller, associate professor of rheumatology at UW-Madison, sees patients with intense pain sensitivity. “There are people with fibromyalgia who come to the clinic … and you ask about pain on a one-to-ten scale, with ten being the worst pain you can imagine, they say ‘I’m at eight or ten,’ as they’re talking calmly and getting up on the table. Their ability to think about pain is skewed toward the high end.”

Perception of physical pain, experts say, is not a simple matter, as it’s affected by multiple factors.

Repeated pain can make some people more sensitive; others, less sensitive. Pain can diminish when we pay attention to something interesting, important or threatening. Drugs and neurotransmitters (chemicals that carry signals in the nervous system) can deaden or enhance pain, and they have different effects in different parts of the brain. Peripheral nerves send pain impulses to the brain, but the brain can also send pain-dampening signals out to the spinal cord.

Muller sees in the clinic this disparity between conditions in the peripheral tissue and reports of pain. “With other people, especially with rheumatoid arthritis, you can see a huge swollen joint, great deformity, but they complain far less, and are far more functional. They push through the pain. This does argue that the pathway to pain is amplified, that the whole concept of pain is skewed.”

Photo of elderly man with buckled hands outstretched to show arthritic fingers.

An elderly gentlemen with arthritic hands. Rheumatoid arthritis can cause long-term pain, but usually without the centralized element that amplifies the sensation of pain.

“The biggest problem in the pain field,” Clauw says, “is recognizing that the most common causes of chronic pain” result from heightened sensitivity, called “centralized pain.” Clauw sees further evidence in the prevalence of such symptoms as fatigue, pain and disorders of memory and sleep in many chronic pain syndromes.

Estimates of the prevalence of chronic pain vary widely. A 2013 study1 asserted that 100 million Americans have chronic pain. German researchers2 found that 19.4 percent of its sample had non-disabling chronic pain, defined by the International Association for the Study of Pain as “pain without apparent biological value that has persisted beyond the normal tissue healing time.” 7.4 percent had disabling chronic pain.

The role of triggers

Battered missile lying on the sand inspected by U.S. military personnel

American veterans of the 1991 Gulf War exhibited Gulf War Syndrome, with many classic symptoms of chronic pain, including fatigue, pain and memory disorders. Exposure to toxic fumes from Iraq’s Scud missiles was cited as a possible cause of Gulf War Syndrome, which is now considered one type of chronic pain. This Scud was intercepted by a U.S. Patriot missile.

Chronic pain often appears after a triggering event, such as an auto accident, infection or fighting in war. A person who develops fibromyalgia after such a trigger “did not start with fibromyalgia,” Clauw says. “That person started with headache, painful menstruation, pain in other areas, and the auto accident was … the final trigger that precipitated the full-blown fibromyalgia. I have never seen a fibromyalgia patient who did not start with regional pain earlier in life, in different areas. They will have headache for couple of years, pain in other areas for a couple of years…. They will move through life with different areas of chronic pain, until some stressor triggers something like fibromyalgia. This is what happened in the first Gulf war; there was an epidemic of chronic pain — called Gulf War Syndrome. I was heavily involved in that research.”

Scientists are starting to detect suggestive signs of chronic pain in the brain. For example, a 2013 study found a volume reduction in 12 brain regions, and an increase in two more, among people with chronic pain. The study concluded that, “Because many of these regions are not classically connected with pain,” these regions may be related to other parts of chronic pain syndromes, including “fatigue and cognitive and emotional impairments.”

Brain scans in a test3 that involved painful stimulation of the forearm showed a loss of density in gray matter in regions of the brain associated with pain processing. The reduction, however, appeared only among subjects who grew more sensitive to pain during the 11-day test; about the same number of people became less sensitive, and their brain density did not change. Because a loss of gray-matter density and growing sensitivity to pain does appear in chronic pain, the researchers speculated that the people who became more sensitive “may have a higher vulnerability to developing chronic pain syndromes.”

Taking drugs

Clauw sees more evidence for the centralized pain hypothesis in drugs that alter brain chemicals, and can treat both psychiatric illness and chronic pain. For example, the antidepressant Cymbalta, “is now effective for chronic lower-back pain, or osteoarthritis,” says Clauw. “It’s not working as an anti-depressant; it’s literally turning down the volume of the pain system” by affecting levels of the neurotransmitter serotonin.

Old photo of mangled automobile, with front axle on the ground

Injured driver and badly damaged car at Kraftwagen Depot, Munich, Germany, June 1915

Other drugs, including opiates, simply fail in centralized pain, Clauw says.

“The idea that there is central sensitization is … as good as we can do right now,” Muller says, but he argues that the portrait of chronic pain is not fully painted. “They talk about pathways, and define them as being important because the medicines work, but it’s not true, they work a tiny bit. I am not convinced that we know a mechanism, or are really close to finding it.”

Chronic pain, Muller says, “is a product of the interaction between genes and the environment,” and the process of sensitization — the triggering event — can sometimes be controlled. People who develop chronic pain, he says, “become canaries in the coal mine that reveal how our society is not set up for the people who have conditions like fibromyalgia and chronic lower-back pain.”

Exercise, meditation and movement

Chronic pain presents treatment dilemmas. Many patients have overlapping complaints and have been taking a variety of drugs for years, even decades. Some have surgeries, even joint replacement, with little relief.

Although some drugs work a bit for chronic pain, many experts prefer to focus on exercise, starting with becoming more active in daily life, walking and swimming. “The few people I have seen who have gotten all their symptoms under control have done it through exercise, mostly aerobic,” says Muller.

Three men in a square pool exercising and stretching with weights.

Naval officers exercise with buoyant dumbbells in a warm therapy pool.

Katie Pumphrey, who aims to swim the English Channel in 2015, began her struggle with chronic pain at age nine. In an interview, she told us that she noticed the benefits of exercise as a member of the high-school swim team. “The less I swam, the more uncomfortable I was. It’s not to say I got better, but I feel I have more control when I exercise. Pain is a lot about mindset. I didn’t really understand that until recently. When a doctor tells you it’s all in your head, or worries that you are making it up, it’s easy to take offense, but in reality it is in your head.”

Pumphrey admits to bad days, and says, “The more my anxiety goes up, the worse my symptoms get. The idea is to tell yourself to calm down, to stay active. For people doing endurance sports in general, there’s a lot of mind over matter.”

And yes, Pumphrey says she’s been in more pain in the two weeks since her 15-mile swim across the Potomac River. “There is a lot of anxiety, panic attacks, moments you want to shake it off, that make you feel crazy,” she says. “But the sense of control over your body, the discovery that your body can do something even though it’s hard, is very helpful for happiness.”

Still she recognizes that few people with chronic pain will follow in her watery footsteps. “This is how I handle pain, it’s not how everyone has to. Being active is important, but everyone has their own limits and needs.”

Hand plucks a small beet from the soil.

Gardening is a low-impact, enjoyable way to increase physical activity for people with or without chronic pain.
Bryce Richter, University Communications, UW-Madison.

What’s your line?

Masataka Umeda, who studies exercise and fibromyalgia as an assistant professor exercise and sport psychology at Texas Tech University, says plenty of questions remain about exercise. “We don’t know the dosage, which is a combination of intensity, duration and frequency, but if you meet a fibromyalgia patient for research or treatment, most patients who show less symptoms are physically active. In study samples, several patients report that they still jog in the neighborhood, walk the dog, walk on a treadmill. On the other side, those who tend to report more symptoms tend to be less physically active, and often are overweight.”

The question is begged: is exercise cause or effect of the better health? “There have been many clinical, randomized trials, and they typically show a beneficial effect of regular exercise on symptoms, which argues against the possibility that [healthier patients] are simply more physically active to start off,” says Umeda.

Both aerobic and anaerobic (resistance) exercise, such as lifting weights, seem to help in chronic pain, Umeda says. Researchers are also finding better effects from other disciplines, such as meditation, yoga and tai chi.

Tai chi, an ancient Chinese system of meditative movement, fulfills the national guidelines for physical activity, says Kristi Hallisy, an assistant professor of physical therapy at UW-Madison. “We know that people with chronic pain should do aerobic exercise, and also neuromuscular training” to improve communication between the central nervous system and the muscles. Balance problems tend to abate from the standing postures in tai chi, she adds. “It’s such a low-level aerobic activity that people who are really deconditioned can tolerate it; it provides leg strength and core body strength.”

Woman calmly performing a tai chi pose.

Tai chi master Tricia Yu demonstrates the tai chi pose “bend bow and shoot tiger. Yu started using tai chi with chronic pain long before it became fashionable. A systematicreview of “meditative movement therapies” (qigong, tai chi and yoga) found improvements in sleep disturbances, fatigue, depression and health-related quality of life, but not in pain.
Photo courtesy Tai Chi Health

Since chronic pain emerges from brains that are overly sensitive to pain, Hallisy says, “By getting somebody in a total body movement program, they can potentially start to remap the brain.”
Exercise may also benefit fatigue, an understudied but significant symptom of fibromyalgia, says Joseph McVeigh, a lecturer at the Institute of Nursing and Health Research at the University of Ulster in the United Kingdom.

A systematic review of earlier work published in 20144 found that exercise reduces fatigue and sleep dysfunction in fibromyalgia. “These are consistently reported to be among the most troubling symptoms of fibromyalgia,” McVeigh wrote to us.

McVeigh also observed that, “In a recent focus group study conducted by ourselves here at the Institute of Nursing and Health Research in the University of Ulster, participants reported that normal physical activities of daily living is sometimes so overwhelming that ‘exercise’ is impossible. Despite the often negative effect of exercise, participants in our study consistently reported that they wanted to engage with exercise and physical activity and many did try to push through the pain. The sense of loss the participants reported at not being able to engage with physical activity (as they previously did) was also quite profound.”

 A woman walks her dog on a footpath next to a lake.

Walking, like many other forms of moderate exercise, can improve physical and mental health in chronic pain.

McVeigh adds that “exercise will have the same beneficial effect on people with fibromyalgia syndrome as it does with us all: cardiovascular effects, reducing the risk of cancer, osteoporosis, managing weight loss and obesity, the positive impact on mood and psychological well-being.”

Beyond the debates about diagnosis and treatment, Muller says chronic pain raises fundamental questions. “Where do we have a place for these people to be successful? There are probably ways we could restructure our society where they could work successfully, but have to be given more time off, more social support, cognitive behavioral therapy, classes in mindfulness meditation, yoga, and these would have to be ongoing.”

In some ways, Muller says, “fibromyalgia is a 2 by 4 upside the head telling you your life has to change. A lot of people, particularly women, take care of others, rather than themselves. It’s often a lifetime of work getting to that place; there is muscle disuse syndrome, they have never exercised, have never had a program of taking care of themselves.

“The whole thing is listen to the story,” Muller adds. “If you do, the patient will tell you what is going on, although that does not mean you can always treat it.”

– David J. Tenenbaum


Kevin Barrett, project assistant; Terry Devitt, editor; S.V. Medaris, designer/illustrator; David J. Tenenbaum, feature writer


  1. Structural Brain Anomalies and Chronic Pain: A Quantitative Meta-Analysis of Gray Matter Volume, Rachel F. Smallwood et al, The Journal of Pain, Vol 14, No 7 (July), 2013: pp 663-675
  2. Untying chronic pain: prevalence and societal burden of chronic pain stages in the general population. Winfried Häuser et al, Häuser et al. BMC Public Health 2014, 14:352
  3. Pain sensitizers exhibit grey matter changes after repetitive pain exposure: A longitudinal voxel-based morphometry study, Anne Stankewitz et al, PAIN 154 (2013) 1732–1737
  4. The Effectiveness of Exercise in the Management of Fatigue and Sleep Dysfunction in Fibromyalgia Syndrome: A Systematic Review, Rheumatology, Volume: 53, supplement 1; 2014
  5. A Soldier’s War on Pain: looking beyond opiates in treating chronic pain
  6. Chronic pain may be genetic, new research suggests
  7. The Perils of Toughing It Out: ignoring pain can lead to a cycle of declining health