The Tell-Tale Brain: A Neuroscientist's Quest for What Makes Us Human

It occurred to me that an evolutionary approach to this problem might be useful. We usually think of pain as a single thing, but from a functional point of view there are at least two kinds of pain. There is acute pain—as when you accidentally put your hand on a hot stove, yelp, and yank your hand away—and then there is chronic pain: pain that persists or recurs over long or indefinite periods, such as might accompany a bone fracture in the hand. Although the two feel the same (painful), they have different biological functions and different evolutionary origins. Acute pain causes you to instantly remove your hand from the stove to prevent further tissue damage. Chronic pain motivates you to keep your fractured hand immobilized to prevent reinjury while it heals.

I began to wonder: If learned paralysis could explain immobilized phantoms, perhaps CRPS-II is a form of “learned pain.” Imagine a patient with a fractured hand. Imagine how, during his long convalescence, pain shoots through his hand every time he moves it. His brain is seeing a constant “if A then B” pattern of events, where A is movement and B is pain. Thus the synapses between the various neurons that represent these two events are strengthened daily—for months on end. Eventually the very attempt to move the hand elicits excruciating pain. This pain may even spread to the arm, causing it to freeze up. In some such cases, the arm not only develops paralysis but actually becomes swollen and inflamed, and in the case of Sudek’s atrophy the bone may even start atrophying. All of this can be seen as a strange manifestation of mind-body interactions gone horribly awry.

At the “Decade of the Brain” symposium that I organized at the University of California, San Diego, in October 1996, I suggested that the mirror box might help alleviate learned pain in the same way that it affects phantom pain. The patient could try moving her limbs in synchrony while looking in the mirror, creating the illusion that the afflicted arm is moving freely, with no pain being evoked. Watching this repeatedly may lead to an “unlearning” of learned pain. A few years later the mirror box was tested by two research groups and found to be effective in treating CRPS-II in a majority of patients. Both studies were conducted double-blind using placebo controls. To be honest I was quite surprised. Since that time, two other double-blind randomized studies have confirmed the striking effectiveness of the procedure. (There is a variant of CRPS-II seen in 15 percent of stroke victims, and the mirror is effective in them as well.)

I’ll mention one last observation on phantom limbs that is even more remarkable than the cases mentioned so far. I used the conventional mirror box but added a novel twist. I had the patient, Chuck, looking at the reflection of his intact limb so as to optically resurrect the phantom as before. But this time, instead of asking him to move his arm, I asked him to hold it steady while I put a minifying (image-shrinking) concave lens between his line of sight and the mirror reflection. From Chuck’s point of view, his phantom now appeared to be about one-half or one-third its “real” size.

Chuck looked surprised and said, “It’s amazing, Doctor. My phantom not only looks small but feels small as well. And guess what—the pain has shrunk too! Down to about one-fourth the intensity it was before.”

This raises the intriguing question of whether even real pain in a real arm evoked with a pinprick would also be diminished by optically shrinking the pin and the arm. In several of the experiments I just described, we saw just how potent a factor vision (or its lack) can be in influencing phantom pain and motor paralysis. If this sort of optically mediated anesthesia could be shown to work on an intact hand, it would be another astonishing example of mind-body interaction.

IT IS FAIR to say that these discoveries—together with the pioneering animal studies of Mike Merzenich and John Kaas and some ingenious clinical work by Leonardo Cohen and Paul Bach y Rita—ushered in a whole new era in neurology, and in neurorehabilitation especially. They led to a radical shift in the way we think about the brain. The old view, which prevailed through the 1980s, was that the brain consists of many specialized modules that are hardwired from birth to perform specific jobs. (The box-and-arrow diagrams of brain connectivity in anatomy textbooks have fostered this highly misleading picture in the minds of generations of medical students. Even today, some textbooks continue to represent this “pre-Copernican” view.)