Woolf was conducting his own experiment in Wall’s lab, applying painful stimuli to rats’ hind legs. The animals developed large “fields” of pain that could easily be activated months later with a light tap or gentle warmth, even in spots that weren’t being touched directly. “I was changing the function of the nervous system, such that its properties were altered,” Woolf says. “Pain was not simply a measure of some peripheral pathology,” he concluded; it “could also be the consequence of abnormal amplification within the nervous system — this was the phenomenon of central sensitization.” Before this discovery, he says, “the feeling was always pain is a symptom that reflects a disease, and now we know that pain often is a consequence of a disease state of the nervous system itself.” Some ailments, like rheumatoid arthritis, can exhibit both peripheral pathology and central sensitization. Others, like fibromyalgia, characterized by pain throughout the body, are considered solely a problem of the central nervous system itself.

A better grasp of how chronic pain changes the central nervous system has emerged since Woolf’s experiment. A.Vania Apkarian’s pain lab at Northwestern University found that when back pain persists, the activity in the brain shifts from the sensory and motor regions to the areas associated with emotion, which include the amygdala and the hippocampus. “It’s now part of the internal psychology,” Apkarian says, “a negative emotional cloud that takes hold.”

The brain itself morphs. Patients with chronic pain can show a significant loss of gray matter in the prefrontal cortex, the attention and decision-making region of the brain that sits behind our foreheads, as well as in the thalamus, which relays sensory signals; both areas are important in processing pain. Excitatory neurotransmitters increase, and inhibitory ones decrease, while glial and other immune cells drive inflammation; the nervous system, unbalanced, magnifies and prolongs the pain. The system goes haywire, like an alarm that keeps blaring even when there’s no threat, even when the pain isn’t protective anymore. Instead, it just begets more pain — and the longer it lasts, the more deeply systemic it becomes and the harder it is to resolve.

There’s a popular saying in neuroscience that as neurons fire together, they begin to wire together, an example of neuroplasticity in action. But if our brains really are plastic, what is shaped there can be reshaped. Therapies that target the brain instead of the aching back or the sore knee — whether through psychology, drugs, direct stimulation of the brain or virtual reality — in theory could undo chronic pain.

In the 1990s, Hunter Hoffman, a cognitive psychologist at the University of Washington, began to use V.R. to provide relief to burn patients who were having their dressings changed — an excruciating ordeal that is difficult to medicate. “Nobody was using virtual reality to reduce the pain of patients before us,” he says. In his V.R. program, called SnowWorld, patients who tumbled through the wintry scene, chucking snowballs at penguins, reported that their relief was similar to what they got from intravenous opioids. Brain scans confirmed these findings: V.R. and opioids each resulted in remarkable reductions in neural activity in pain-related areas.

Unlike most drugs and surgical procedures, V.R. has far fewer side effects — mostly nausea and motion sickness. Headsets now cost a fraction of what they once did, and graphics are markedly improved, resulting in more immersive experiences and fewer potential side effects. What’s more, Hoffman says, “all the major computer companies are pumping billions of dollars into virtual reality as a kind of internet” — what Mark Zuckerberg called an “embodied internet” when he announced last fall that Facebook was becoming Meta. A few months later, Microsoft unveiled plans to acquire Activision Blizzard to “provide building blocks for the metaverse,” the company said. The downstream effects of all this technological ferment, Hoffman predicts, is that V.R. therapies, powered by private-sector investments, will swiftly develop into a standard treatment for pain.

On Aug. 8, 2016, Robert Jester, a retired high school biology teacher in Greenport, N.Y., who was moonlighting as a chimney sweeper — both to support his family and to enjoy the magnificent views — drove to a nearby neighborhood for a quick job. The ladder he took was too short, but it seemed like a simple sweep, so he decided to go ahead with the work anyway. He climbed to the top, the ladder slipped — and he fell to the hard ground below. The pain in his back was so intense that he couldn’t make out the rescue workers bending over him; he could see only white light.