The Pain Chronicles (34 page)

One might expect the experience of pain to compel a unique focus of attention on the body. But religious devotees insist that during certain rites, this focus paradoxically metamorphoses into its opposite: a feeling of transcending or being freed from the body. Ascetics describe the moment during mortification when pain becomes no-pain—when, as a pilgrim put it, “Pain, having become so intense, began to disappear,” or, as a mystic wrote, “At one moment everything is pain; but at the next moment, everything is love.”

How does pain cause the brain to create this sense of dislocation from one’s own body? The Canadian psychologist Ronald Melzack (the coauthor of the McGill Pain Questionnaire) theorized that each person has a unique “neurosignature” (the neural relay of the thalamus, cortex, and limbic system that constitutes the neuromatrix). The neurosignature creates what he calls a “body-self neuromatrix” that integrates the continuous flow of sensory input into a conscious awareness of oneself. Intense pain, he speculated, overwhelms the neuromatrix with an excess of sensory information, interrupting the neurosignature and arresting the body-self template. Although the sensation of pain continues to register, it can no longer be processed. One remains aware of the pain but ceases to experience that pain as belonging to oneself—or, indeed, ceases to experience a self for pain to belong to. This phenomenon is “either terrifying or exhilarating,” Ariel Glucklich writes, depending on whether it was sought or not.

I remember watching the impassive face of the devotee at Thaipusam as the priest threaded the fishhooks with the dangling limes through his back and how he had said the pain no longer belonged to him. The god freed him from pain.

Distracted by thinking about hyperstimulation analgesia—and then distracted by thinking about Tracey’s theory of the modulating effects of distraction—I watch as my rACC activation dwindles to nothing.

COGNITIVE CONTROL OVER NEUROPLASTICITY

The results of my scan, Sean Mackey tells me a few days later, indicate that I have significant control of my brain activity. A week later I am scanned again, in the sleek office at Omneuron, a Menlo Park medical-technology company Christopher deCharms founded to develop clinical applications of real-time functional neuroimaging. This time, it feels easier to control my rACC with less reliance on elaborate fantasy; I am interacting more directly with my brain.

This learning effect was demonstrated by a study they published in the prestigious
Proceedings of the National Academy of Sciences.
The study showed that while looking at images of their own brains’ activity, subjects can learn to control the activation in a way that significantly regulates their pain. The first phase of the study looked at thirty-six healthy subjects and twelve with chronic pain. In the scanner, the healthy ones tried to modulate their responses to a painful heat stimulus. The chronic pain patients, however, worked to reduce only the pain they already felt. The chronic pain patients who received neuroimaging training reported an average decrease of 64 percent in their pain rating by the end of the study. Moreover, the benefit of the study continued after it was over: a majority of the pain patients reported that they continued to experience a reduction of pain by 50 percent or more. Healthy subjects also reported a significant increase in their ability to control the pain during the study.

“One big concern we had,” Dr. Mackey says, “was: Were we creating the world’s most expensive placebo?” To make sure that wasn’t the case, he trained a control group in pain-reduction techniques without using the scanner (as in his previous experiment) to see if that was as effective as employing a multimillion-dollar machine. He also tried scanning subjects without showing them their brain images—and he tried tricking subjects by feeding them images of irrelevant parts of their brains or feeding them someone else’s brain images. “None of these worked,” Dr. Mackey says, “or worked nearly as well.” Traditional biofeedback also compared unfavorably: changes in pain ratings of subjects in the neuroimaging therapy group were three times as large as in the biofeedback control group.

Subsequent phases of the study will assess whether the technique offers long-term practical benefits to a larger group of chronic pain patients by fundamentally changing their modulatory systems so that they can reduce pain all the time without constantly and consciously trying to do so. If they can, then the technique would not merely provide shelter from the storm of pain; it would bring about climate change. Unpublished work found that repeated training over six weeks of subjects with chronic pain significantly reduced their pain.

“I believe the technique could make lasting changes because the brain is a machine designed to learn,” Dr. deCharms says. The brain is plastic: whenever you learn something, new neural connections form, and old, unused ones wither away (a process known as
activity-dependent neuroplasticity
). Thus, engaging a certain brain region can alter it. (Neuroimaging has shown, for example, that the part of the brains of London cabdrivers that deals in spatial relations is larger than usual. More strikingly, after merely three months of training, learning to juggle creates visible changes in parts of the brain involved with motor coordination.)

Many diseases of the central nervous system involve inappropriate levels of activation in particular brain regions that change the way they operate. Some regions experience less activity, and other regions become hyperactive. (For example, epilepsy involves abnormal hyperactivity of cells; stroke, Parkinson’s, and other diseases involve neurodegeneration.) In the case of chronic pain, new nerve cells, recruited for transmitting pain, create more pain pathways in the nervous system, while nerve cells that would normally inhibit or slow the signaling begin to decrease or function abnormally. Neuroimaging therapy may mitigate this harm by teaching people how to increase the efficacy of their healthy brain cells.

“It gives people a tool they didn’t know they had,” Dr. Mackey says. “Cognitive control over neuroplasticity.”

The technique may offer a particular advantage over drug therapy. It is difficult to design drugs to change a disease process in a specific region of the brain, because drugs work by targeting receptors, and most receptors, such as opiate receptors, are present in multiple systems throughout the brain and body (one reason such drugs almost always have side effects). Neuroimaging therapy, by contrast, is anatomically specific, allowing for the possibility of targeted neuroplasticity, much as a muscle can be isolated and trained.

Neuroimaging therapy “provides tangible evidence that people can change their own brains, which can be very empowering,” Dr. Mackey says. Much as people were once puzzled by Freud’s talking cure (how could describing problems
solve
them?), the idea of a “looking cure,” as it were, makes us wonder: How could one part of our brain control another, and why would
looking
at the process help to do so? Who, then, is the “me” controlling my brain? The technique seems to deepen—rather than resolve—the mind-body problem, widening the Cartesian divide by splitting the self into agent and object, mind and brain, ghost and machine.

“The decision-making parts of the brain are thought to be the prefrontal regions of the cortex,” Dr. Mackey says. But as for how those brain parts
cause
the change in the rACC—“Heck if I know! How do we get the brain to do
anything
? We can map out the anatomical circuits involved and the general functions of those circuits, but we can’t tell you the mechanism by which any cognitive decision—large or small—is translated into action.”

Neuroimaging therapy as a treatment for disease is one of those novel ideas that seems obvious in retrospect, but no one thought to try before. Although some researchers have experimented with teaching subjects to control their brain activation to create a “brain-computer interface,” the purpose of those experiments has been theoretical rather than therapeutic. In one such experiment, for example, subjects were taught to navigate a cursor through a maze on a screen using only their brains. Subjects completed a sequence of mental strategies. Each strategy activated a different part of the brain that automatically moved the cursor a different way. By observing how certain activations resulted in corresponding movements of the cursor, subjects were able to learn how to navigate the cursor through the maze.

Perhaps the best example of a “looking cure” is a novel treatment for phantom limb pain. The neurologist Vilayanur S. Ramachandran used a mirror box (a box with two mirrors in the center, one facing each way), in which patients put their actual limb in one side and their stump in the other. When patients move their actual limb, looking in one side of the mirror box, they appear to be moving both arms. Phantom limb pain typically involves the sensation that the phantom arm is stuck in an uncomfortable position. By straightening her existing arm in the mirror box, a patient can have the illusion of uncurling her phantom arm, and the cramping pain goes away. (More recently, scientists from the University of Manchester have had success using a computer-generated simulation to create a more realistic-looking illusion.)

Since patients know it is an illusion, why does the trick help? Through an unknown mechanism, the visual cortex communicates the image to the somatosensory cortex, which somehow decides to mimic the image in the mirror by making the phantom limb relax. Phantom limb pain is theorized to derive from the neural reorganization in the somatosensory cortex. Functional imaging has shown that repeated use of the mirror can reverse those changes and reduce pain. Although more extensive trials are needed, repeated training has shown long-term improvements in some patients.

TERRA INCOGNITA

One of the limitations of pain treatment today is that pain presents the same symptom regardless of how it is generated or what type of pain it is, yet different conditions require different treatment. Brain imaging might be used diagnostically for individual patients, to determine the nature of their pain. It might also spur the development of more targeted pain drugs.

Irene Tracey—who directs Oxford University’s brain imaging center in England and is a rising star in the field—believes that brain imaging could also be useful in medical malpractice and disability court cases to document the reality of the pain of a plaintiff. These cases are currently hampered by the lack of an objective measure of pain, leaving juries at a loss how to distinguish between honest plaintiffs and malingerers.

The Gothic kingdom of Oxford seemed gloomy in the late November afternoon as I made my way to Dr. Tracey’s office. But inside, everything began to seem brighter. Her cheeks flushed as she discussed the future of her research. “In five to ten years,” she said definitively, “we will be able to put someone in a scanner and say, ‘Your pain comes 10 percent from hypervigilance [paying too much attention to the pain], 20 percent from catastrophizing [excessive worry], 20 percent from peripheral input [from the original injury or disease], and 50 percent from brain circuit dysfunction.’ We can already scan people and tell them far more about their pain than they can tell us,” she concluded crisply.

Beneath her pale blouse, with its pattern of tiny flowers, the swell of her third child was just visible. I pictured the fetus’s brain cells dividing into neural networks in a design that would one day be known. One day, too, would my pain be known because imaging would identify each of the elements of which it is composed? Would the mystery of pain, then, finally be unveiled?

Three years later I write to Dr. Tracey, asking her to update me on her work. Since so much time had elapsed, I expect her to tell me that we are much closer to achieving her vision of using brain imaging to identify different kinds of pain. But instead she is much more circumspect. “In five to ten years, we
might
be able to put someone in a scanner and say, ‘Your pain comes from a combination of hypervigilance . . .’ ” she writes.

I object that the conditional makes the prediction meaningless (after all, anything “
might
” happen . . . aliens might bring us pain-scanning technology), to no avail. She also writes that the idea of assigning an actual percentage to the different kinds of pain in a sufferer’s mind sounds “amateur” because “all these factors are interactive, you see . . .”

I recall how Ari (the Israeli artist who suffered from migraines and fibromyalgia) had asked me if I believed there would be a cure for chronic pain. “Oh yes,” I’d said. There had been an inspiring update to the crushing study on chronic pain shrinking the gray matter of the brain. A German research group found that when patients who had suffered from chronic hip pain got a total hip replacement, their gray matter regenerated, suggesting that the shrinkage that had been observed did not stem from neuronal loss, which is irreversible, but merely from a change in the size of cells. So, perhaps the damage of all chronic pain syndromes could be reversed. Perhaps, too, one day, chronic pain would be controlled just as acute pain can be controlled through anesthesia, and anyway, no one would develop chronic pain in the future, because pain would be treated at its onset. I launched into my pet analogy of TB and how pain clinics would all fold up shop like the sanatoriums. As I talked, I had an image of the consumptives packing their suitcases on the magic mountain, the directors discussing whether to turn it into a museum.

“One day . . .” Ari drawled, “in the next millennium?”

I hesitated.

“Let me put it this way,” he said. “If you were a venture capitalist, would you invest in a company whose mission was to find a cure for chronic pain?”

I recalled the catch in my optimistic analogy: the lag time—the half century between the discovery of the tuberculosis bacterium and the discovery of antibiotics. And pain is not a simple bacterium, visible under a microscope, but a complex aspect of consciousness. The tools to look at the brain have only just been invented, and the brain itself is still mainly terra incognita—more like the ancient maps of faraway lands than like Google Earth. Would the discoveries of pain-related genes lead to the development of effective drugs soon? For how many years will the critical breakthrough about pain remain five to ten years hence?

“Not if I wanted to get rich quickly,” I conceded.

“How’s your pain?” he asked.

I never knew how to respond to that question. Okay. Better than it used to be. Bearable, almost never unbearable. But still there—always. Since my arthritic condition is degenerative, presumably it has degenerated further over the years, but I do not have more pain now—I have less—and for that I am grateful and thrilled. It’s so hard to know the best attitude to assume! On the one hand, I want to be satisfied with the progress I’ve made: to accept the balance of pain that remains and close the pages of my pain diary forever. On the other hand, to fully accept it feels as if I am settling for a pained life. I want to keep a candle in the window of my mind for my pathography to have something besides a philosophical ending.

In the three years I’ve been married, though, I’ve been surprised to discover that my wishes have changed. On my first birthday after our wedding, I wished to have a child and realized that I wanted that more than I wanted not to have pain, and that if the Wish Fairy would grant only one wish, I’d choose the child. (Of course, if my pain worsened, that could change, I hastened to let the Wish Fairy know, lest she think I had forgotten how compelling pain can be.)

The next birthday I wished for a baby again. But on my last birthday, I had a new wish: that the twins with whom—through the miracle of medical science—we were about to be twice blest would be healthy, that their new bodies would be gifted with the pain-protective gene variant and spared the pain-sensitivity gene variant, and that their lives would not be blighted by persistent pain.