The neuroscience of pain


On a foggy February morning in Oxford, England, I arrived at the John Radcliffe Hospital, a shiplike nineteen-seventies complex moored on a hill east of the city center, for the express purpose of being hurt. I had an appointment with a scientist named Irene Tracey, a brisk woman in her early fifties who directs Oxford University’s Nuffield Department of Clinical Neurosciences and has become known as the Queen of Pain. “We might have a problem with you being a ginger,” she warned when we met. Redheads typically perceive pain differently from those with other hair colors; many also flinch at the use of the G-word. “I’m sorry, a lovely auburn,” she quickly said, while a doctoral student used a ruler and a purple Sharpie to draw the outline of a one-inch square on my right shin.

Wearing thick rubber gloves, the student squeezed a dollop of pale-orange cream into the center of the square and delicately spread it to the edges, as if frosting a cake. The cream contained capsaicin, the chemical responsible for the burn of chili peppers. “We love capsaicin,” Tracey said. “It does two really nice things: it ramps up gradually to become quite intense, and it activates receptors in your skin that we know a lot about.” Thus anointed, I signed my disclaimer forms and was strapped into the scanning bed of a magnetic-resonance-imaging (MRI) machine.

The machine was a 7-Tesla MRI, of which there are fewer than a hundred in the world. The magnetic field it generates (teslas are a unit of magnetic strength) is more than four times as powerful as that of the average hospital MRI machine, resulting in images of much greater detail. As the cryogenic units responsible for cooling the machine’s superconducting magnet clicked on and off in a syncopated rhythm, the imaging technician warned me that, once he slid me inside, I might feel dizzy, see flashing lights, or experience a metallic taste in my mouth. “I always feel like I’m turning a corner,” Tracey said. She explained that the magnetic field would instantly pull the proton in each of the octillions of hydrogen atoms in my body into alignment. Then she vanished into a control room, where a bank of screens would allow her to watch my brain as it experienced pain.

During the next couple of hours, I had needles repeatedly stuck into my ankle and the fleshy part of my calf. A hot-water bottle applied to my capsaicin patch inflicted the perceptual equivalent of a third-degree burn, after which a cooling pack placed on the same spot brought tear-inducing relief. Each time Tracey and her team prepared to observe a new slice of my brain, the machine beeped, and a small screen in front of my face flashed the word “Ready” in white lettering on a black background. After each assault, I was asked to rate my pain on a scale of 0 to 10.

Initially, I was concerned that I was letting the team down. The capsaicin patch hardly tingled, and I scored the first round of pinpricks as a 3, more out of hope than conviction. I needn’t have worried. The patch began to itch, then burn. By the time the hot-water bottle was placed on it, about an hour in, I was surely at an 8. The next set of pinpricks felt as if I were being run through with a hot metal skewer.

“You’re a good responder,” Tracey told me, rubbing her hands together, when I emerged, dazed. “And you’ve got a lovely plump brain—all my postdocs want to sign you up.” As my data were sent off for analysis, she pressed a large cappuccino into my hands and gently removed the capsaicin with an alcohol wipe.

Tracey didn’t need to ask me how it had gone. The imaging-analysis software, designed in her department and now used around the world, employs a color scale that shades from cool to hot, with three-dimensional pixels coded from blue through red to yellow, depending on the level of neural activity in a region. Tracey has analyzed thousands of these “blob maps,” as she calls them—scans produced using a technique called functional magnetic resonance imaging (fMRI). Watching a succession of fiery-orange jellyfish flaring up in my skull, she had seen my pain wax and wane, its outlines shifting as mild discomfort became nearly unbearable agony.

For scientists, pain has long presented an intractable problem: it is a physiological process, just like breathing or digestion, and yet it is inherently, stubbornly subjective—only you feel your pain. It is also a notoriously hard experience to convey accurately to others. Virginia Woolf bemoaned the fact that “the merest schoolgirl, when she falls in love, has Shakespeare or Keats to speak her mind for her; but let a sufferer try to describe a pain in his head to a doctor and language at once runs dry.” Elaine Scarry, in the 1985 book “The Body in Pain,” wrote, “Physical pain does not simply resist language but actively destroys it.”

The medical profession, too, has often declared itself frustrated at pain’s indescribability. “It would be a great thing to understand Pain in all its meanings,” Peter Mere Latham, physician extraordinary to Queen Victoria, wrote, before concluding despairingly, “Things which all men know infallibly by their own perceptive experience, cannot be made plainer by words. Therefore, let Pain be spoken of simply as Pain.”

But, in the past two decades, a small number of scientists have begun finding ways to capture the experience in quantifiable, objective data, and Tracey has emerged as a formidable figure in the field. By scanning several thousand people, healthy and sick, while subjecting them to burns, pokes, prods, and electric shocks, she has pioneered experimental methods to survey the neural landscape of pain. In the past few years, her work has expanded from the study of “normal” pain—the everyday, passing experience of a stubbed toe or a burned tongue—to the realm of chronic pain. Her findings have already changed our understanding of pain; now they promise to transform its diagnosis and treatment, a shift whose effects will be felt in hospitals, courtrooms, and society at large.

The history of pain research is full of ingenious, largely failed attempts to measure pain. The nineteenth-century French doctor Marc Colombat de l’Isère evaluated the pitch and rhythm of cries of suffering. In the nineteen-forties, doctors at Cornell University used a heat-emitting instrument known as a “dolorimeter” to apply precise increments of pain to the forehead. By noting whenever a person perceived an increase or decrease in sensation, they arrived at a pain scale calibrated in increments of “dols,” each of which was a “just-noticeable difference” away from the adjacent dols. Last year, scientists at M.I.T. developed an algorithm called DeepFacelift, which attempts to predict pain scores based on facial expressions.

The most widely adopted tools rely on the subjective reports of sufferers. In the nineteen-fifties, a Canadian psychologist named Ronald Melzack treated “an impish, delightful woman in her mid-seventies” who suffered from diabetes and whose legs were both amputated. She was tormented by phantom-limb pain, and Melzack was struck by her linguistic resourcefulness in describing it. He began collecting the words that she and other patients used most frequently, organizing this vocabulary into categories, in an attempt to capture pain’s temporal, sensory, and affective dimensions, as well as its intensity. The result, published two decades later, was the McGill Pain Questionnaire, a scale comprising some eighty descriptors—“stabbing,” “gnawing,” “radiating,” “shooting,” and so on. The questionnaire is still much used, but there have been few surveys of its efficacy in a clinical setting, and it’s easy to see how one person’s “agonizing” could be another person’s “wretched.” Furthermore, a study by the sociologist Cassandra Crawford found that, after the questionnaire’s publication, clinical descriptions of phantom-limb pain shifted dramatically, implying that the assessment device was, to some extent, informing the sensations it was intended to measure.

Meanwhile, as the historian Joanna Bourke has shown, in her book “The Story of Pain,” attempts to translate the McGill Pain Questionnaire into other languages have revealed the extent to which cultural context shapes language, which, in turn, shapes perception. In mid-century Montreal, Melzack’s talkative diabetic might have described a migraine as lacerating or pulsing, but the Sakhalin Ainu traditionally rated the intensity of pounding headaches in terms of the animal whose footsteps they most resembled: a bear headache was worse than a musk-deer headache. (If a headache was accompanied by a chill, it was described with an analogy to sea creatures.)

“I feel like I have all this anger inside but no one special to share it with.”
By far the most common tool used today to measure pain is the one I employed in the scanner: the 0-to-10 numerical scale. Its rudimentary ancestor was introduced in 1948, by Kenneth Keele, a British cardiologist, who asked his patients to choose a score between 0 (no pain) and 3 (“severe” pain). Over the years, the scale has stretched to 10, in order to accommodate more gradations of sensation. In some settings, patients, rather than picking a number, place a mark on a ten-centimetre line, which is sometimes adorned with cheerful and grimacing faces.

In 2000, Congress declared the next ten years the “Decade of Pain Control and Research,” after the Supreme Court, rejecting the idea of physician-assisted suicide as a constitutional right, recommended improvements in palliative care. Pain was declared “the fifth vital sign” (alongside blood pressure, pulse rate, respiratory rate, and temperature), and the numerical scoring of pain became a standard feature of U.S. medical records, billing codes, and best-practice guides.

But numerical scales are far from satisfactory. In Tracey’s MRI machine, my third-degree burn felt five points more intense than the initial pinpricks, but was it really only two points less than the worst I could imagine? Surely not, but, having never given birth, broken any bones, or undergone serious surgery, how was I to know?

The self-reported nature of pain scores leads, inevitably, to their accuracy being challenged. “To have great pain is to have certainty,” Elaine Scarry wrote. “To hear that another person has pain is to have doubt.” That doubt opens the door to stereotyping and bias. The 2014 edition of the textbook “Nursing: A Concept-Based Approach to Learning” warned practitioners that Native Americans “may pick a sacred number when asked to rate pain,” and that the validity of self-reports will likely be affected by the fact that Jewish people “believe that pain must be shared” and black people “believe suffering and pain are inevitable.” Last year, the book’s publisher, Pearson, announced that it would remove the offending passage from future editions, but biases remain common, and study after study has shown shocking disparities in pain treatment. A 2016 paper noted that black patients are significantly less likely than white patients to be prescribed medication for the same level of reported pain, and they receive smaller doses. A group of researchers from the University of Pennsylvania found that women are up to twenty-five per cent less likely than men to be given opioids for pain.