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Pain, Pain Go Away

By Dale Keiger
Pain afflicts millions of lives and costs millions of dollars. Treating it has proved to be extraordinarily hard.
I hurt, you hurt, we all hurt. Pain is a human constant. Today it’s the minor burn suffered while searing last night’s pork chops. Tomorrow it’s a twinge in the lower back. Or the faint pulse of an incipient headache, the sting of a hangnail, or the constant tormenting aftermath of a neck injury that drains life of all joy. 
In its 2011 report Relieving Pain in America, the Institute of Medicine of the National Academy of Sciences estimated that 100 million American adults suffer from chronic pain. That’s more than the number of adults with heart disease, cancer, and diabetes combined. Those numbers don’t include people suffering from acute pain, defined as pain that disappears when the underlying cause has been treated or healed. Nor do the figures include children. And public health researchers believe the problem is getting worse. A report issued in 2009 by the United Kingdom Department of Health stated, “Chronic pain is two to three times more common now than it was 40 years ago.” 
“I hate pain. I’m petrified of pain,” says Allan Belzberg, clinical director of the Neurosurgery Pain Research Institute and an associate professor of neurological surgery at Johns Hopkins. “I can take out a brain tumor, I can take out a nerve tumor, I can fix a spine and I help those people, no question. But when I have patients who have chronic pain and I can help them with that, that is a dramatic change in their lives. I feel ashamed and horrific when I can’t help someone who’s in pain.”
The contemporary science of pain and its alleviation is a sophisticated multidisciplinary endeavor. At Johns Hopkins, neurologists, psychologists, psychiatrists, surgeons, geneticists, anesthesiologists, electrophysiologists, nursing researchers, and molecular biologists all work on pain. But there remains much that mystifies scientists. “Pain biology is really taking off,” says James Campbell, a Johns Hopkins professor emeritus of neurosurgery. 
“But pain therapeutics is limping along. There are too many people walking around who would say their pain level is six, seven, or eight on a zero-to-10 scale. If we can put a man on the moon, why should anyone have to walk around with a pain level of eight?”

That medicine struggles to alleviate pain is testament to how complex it is as a physiological and psychological phenomenon. Jab your finger with a pin. The body’s first reaction comes when the point of the pin stimulates a nerve fiber in your fingertip. The fiber is part of a pain sensor known as a nociceptor. When your fingertip is jabbed, the activated nociceptor shoots an electrical impulse along the length of your arm, past a cluster of cells in the spinal cord called the dorsal horn. In the dorsal horn, the nerve impulse gets processed into the spinal cord. Neurons in the spinal cord send the signal up to the thalamus, deep in the core of the brain. Finally, the thalamus relays the information that your finger has been pricked to the somatosensory cortex (which senses it), the frontal cortex (which thinks about it), and the limbic system (which reacts to it emotionally). Ouch.

In textbooks and on medical websites, this series of steps is often represented by an infographic that portrays the nervous system as a sort of electrical circuit. Viewed this way, pain seems simple and straightforward. But the neat diagram doesn’t even hint at the baffling complexity of pain, says Jennifer Haythornthwaite, a professor of psychiatry and behavioral sciences in the School of Medicine. So much more is going on, even with a minor injury. For example, make the wound a bit more severe than a pinprick—say, a cut that requires a few stitches. The sliced tissue hurts at the point of the injury. That makes sense—the knife that slipped while you were cutting carrots damaged nerves in your finger. But the next day, the pain has expanded to an area around the cut, which is inflamed. That tissue was not injured, yet it hurts. Why? Make the injury worse again—now say the finger’s been broken in a softball game. The fracture hurts because, as with the cut, tissues and nerves around the damaged bone have suffered trauma. Eight weeks later, everything regarding the bone has mended properly, but pain persists. Why, if the bone and nerves have apparently healed, do you still hurt?
The complexities do not end there. If you are African-American, you will feel pain more than if you are a non-Hispanic Caucasian. This is not a subjective matter; laboratory research has documented that pain sensitivity is generally higher in blacks. In the same way, women generally are more pain-sensitive than men. In demonstrative cultures, people respond to pain with more emotional distress than people in stoic cultures. And that circuit diagram of pain does nothing to represent what happens in the brain, where physical perception becomes pain and often develops into the psychological phenomenon of suffering. “You can give 10 people in the lab the same stimulus and get 10 different responses and see 10 different brain images,” says Haythornthwaite.
That circuit diagram of pain does nothing to represent what happens in the brain, where physical perception becomes pain and often develops into the psychological phenomenon of suffering.

Haythornthwaite estimates that Johns Hopkins has, cumulatively, one of the four or five biggest pain research efforts in the country. An important nexus at Hopkins is the Blaustein Pain Treatment Center. There is also the Neurosurgery Pain Research Institute, a new initiative housed in the School of Medicine’s Department of Neurosurgery. Michael Caterina directs the institute. “Pain involves a lot of learning on the part of the nervous system,” Caterina says. 

“A lot of changes happen when you injure a nerve or injure the tissue that the nerve innervates.” When, for example, the pain stimuli are pronounced and persistent, that experience seems to change the strength of the impulses flowing through the nervous system, like an amplifier, and the change lasts for a long time. If a period of sustained pain can change how your spinal cord functions, an effective therapy will have to do a lot more than just dampen the hurt of the original injury.
As pain scientists develop an ever more granular understanding of pain, they get closer to explaining the baffling inconsistency and seeming illogic of pain as a physiological phenomenon. For example, Caterina cites the work of Johns Hopkins neurologists Justin McArthur and Michael Polydefkis, who have been taking skin biopsies from people experiencing pain from conditions such as diabetic neuropathy and shingles. They have found, in these patients, a marked reduction in the number of nerve endings in the biopsied skin. How is it that people with fewer nerve fibers have more pain? The researchers are testing several theories to better understand why that might be, but at this point we still don’t know. 
It’s important to remember that  “pain is not just a biological experience,” according to Haythornthwaite. “It is a psychological experience as well as a sociocultural experience.” Haythornthwaite works on pain-related catastrophizing—a particular cognitive and emotional response to pain. Some people hurt and stoically carry on. In catastrophizers, pain overwhelms them. The condition correlates with other psychological conditions like neuroticism and depression. 
“So much of what we do for a patient depends on believing the patient.”
When someone in pain shows up in an emergency room, how physicians and nurses respond to them affects not only the patient’s psychological state but also their physical sensitivity. “People come to pain with a history of experiences that mold and shape their perception of pain at that moment,” says Haythornthwaite.
Inner-city hospitals like Johns Hopkins see a lot of patients with substance abuse problems in their emergency rooms. The response of clinical staff there can exacerbate pain. Campbell, who helped start the Blaustein Pain Treatment Center at Hopkins, says it is hard to distinguish whether a patient has been abusing drugs and wishes to score pain meds or is truly in pain. “We still don’t have a handle on that,” Campbell says. “So much of what we do for a patient depends on believing the patient. If you don’t believe the patient, it becomes a really frustrating encounter. Imagine it from the patient’s perspective. You have pain, and your doctor doesn’t believe you. What a double whammy that is.” 
The sociocultural and emotional component of pain may be one part of the frustrating failure of so many therapeutics that seem to work in the lab on animals, then flop in clinical trials. Researchers can measure the physical response of a mouse to a pharmaceutical compound, but a mouse can’t describe its mood, can’t report that it slept badly the night before, can’t express symptoms of depression—aspects of suffering that accompany chronic pain. For this reason, pain researchers at Johns Hopkins and elsewhere have begun to add to their experimental repertoire more sophisticated methods that allow the animal to indicate to the investigator, based on its actions, whether a particular intervention makes it less uncomfortable. 
The challenge with pain medication is that “different drugs work in different people,” Campbell observes.  “What one sees over and over again is that a particular drug therapy works great in one person but fails miserably in another. Drug trials typically measure the average response and miss out on individual responses. As a result, some drugs fail to gain FDA approval even though they may be safe and effective in certain people. What is needed are ways to predict what the best therapy is for a particular individual, rather than simply depending on an empirical trial of a drug.”
Campbell had an idea several years ago: What if pain became the “fifth vital sign”? In a hospital, staff evaluate four vital signs to monitor a patient’s condition: breathing, pulse, blood pressure, and temperature. Campbell started a national campaign to make the presence and degree of pain a fifth component in the routine assessment of a patient’s condition; he says the practice has since been widely adopted across the medical landscape. As he stated in his 1996 presidential address to the American Pain Society: “Vital signs are taken seriously. If pain were assessed with the same zeal as other vital signs are, it would have a much better chance of being treated properly. We need to train doctors and nurses to treat pain as a vital sign.”
There is an arsenal of pain medications now, some of them effective for short-term treatment of acute pain. Long-term use for chronic pain is more complicated because the body builds tolerance to drugs like morphine and oxycodone and develops physical dependency. Michael Clark, the director of pain treatment programs at Johns Hopkins Medicine, says physicians need to be better educated about pain therapeutics. “People would benefit from the ABCs, the basics,” he says.  “‘Here are the drugs, here’s how you prescribe.’ Five hours of that would translate into a lot more patients treated well.”
Beth Murinson, an associate professor in the Johns Hopkins School of Medicine, has done significant work on better education of medical students in pain management. “This is a big topic for us,” she says. “We have built a much more robust program in pain for Hopkins medical students. What should a Hopkins medical student know about pain by the time of graduation? We developed 255 learning objectives. We used these as the foundation for a survey of North American medical schools, and results of this work were included in Relieving Pain in America. In that study, we found that most medical schools, over four years of instruction, are devoting less than 10 hours to pain. This is a huge deficit in light of the observation that over 100 million Americans suffer with pain, and the additional observation that about half of medical encounters involve patients with pain. We interpreted this to mean that most practitioners are simply not equipped to address a very common clinical occurrence: pain and the varieties thereof.”
“Nurses tell us all the time that if the doctor goes in and holds the patient’s hand and asks them how they are, the nurse will have fewer complaints from the patient.”
Sometimes the most effective treatment regimen involves things patients do not want to do. “No matter what, the overall long-term success rate for injections, for operations, for medications, tends to be low,” says Steven Cohen, director of the Blaustein Pain Treatment Center. “The things that we know work—if you’re obese, losing weight; if you’re sedentary, exercise—nobody wants to hear. Nobody wants to come into the pain clinic and hear, ‘Lose weight and exercise more.’ People want a pill. A lot of them want narcotics.”
Amid all the sophisticated science and discussion of pain’s remarkable complexity, it is easy to overlook a far more basic form of therapy. Belzberg points to studies that demonstrate the remarkable effect of someone simply asking the patient how he or she feels. “Nurses tell us all the time that if the doctor goes in and holds the patient’s hand and asks them how they are, the nurse will have fewer complaints from the patient,” he says. “No question. Nurses have been telling us this for years.” It doesn’t have to be a doctor doing this, Belzberg says. Patients report more satisfaction with their pain management when anybody asks how they’re doing, even a member of the housekeeping staff.
“In talking to patients and trying to get a handle on this,” Belzberg says, “one thing that becomes very clear is that for somebody who is in pain, they want to know that you are listening to them, that you’re willing to help. You’re willing to listen and try to understand what it is that they are suffering. 
Pain, Pain Go Away
Francesco Bongiorni
James Campbell started a national campaign to make the presence and degree of pain a fifth component in the routine assessment of a patient’s condition. The practice has been widely adopted across the medical landscape. 

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