Woolf was conducting his experiment in Wall’s lab, applying painful stimuli to the hind legs of mice. The animals developed large “fields” of pain that could be easily activated months later with a light touch or a light heat, even in places that were not directly touched. “I was changing the function of the nervous system so that its properties were altered,” Woolf says. “Pain was not simply a measure of some peripheral pathology,” she concluded; it could also be the consequence of an abnormal amplification within the nervous system: this was the phenomenon of central sensitization. Prior to this discovery, she says, “the feeling of having always been pain is a symptom that reflects a disease, and we now know that pain is often a consequence of a pathological state of the nervous system itself.” Some disorders, such as rheumatoid arthritis, can have both peripheral pathology and central sensitization. Others, such as fibromyalgia, which is characterized by pain throughout the body, are considered solely a problem of the central nervous system itself.
A better understanding of how chronic pain changes the central nervous system emerged from Woolf’s experiment. Vania Apkarian’s pain laboratory at Northwestern University found that when back pain persists, activity in the brain shifts from sensory and motor regions to areas associated with emotion, which include the amygdala and the hippocampus. “Now it’s part of the internal psychology,” says Apkarian, “a negative emotional cloud taking hold.”
The brain itself transforms. Patients with chronic pain may show significant loss of gray matter in the prefrontal cortex, the attention and decision-making region of the brain that lies behind our foreheads, as well as in the thalamus, which transmits sensory signals; both areas are important in pain processing. Excitatory neurotransmitters increase and inhibitory neurotransmitters decrease, while glial cells and other immune cells drive inflammation; the nervous system, unbalanced, amplifies and prolongs the pain. The system goes haywire, like an alarm that continues to sound even when there is no threat, even when the pain is no longer protective. Instead, it only generates more pain and the longer it lasts, the more deeply systemic it becomes and the harder it is to fix it.
There is a popular saying in neuroscience that when neurons fire together, they begin to bind together – an example of neuroplasticity in action. But if our brains are really plastic, what is molded there can be reshaped. Therapies that target the brain instead of aching back or aching knee, whether through psychology, medications, direct brain stimulation, or virtual reality, could theoretically nullify chronic pain.
In the 1990s, Hunter Hoffman, a cognitive psychologist at the University of Washington, began using virtual reality to provide relief for burn patients who were changing their dressings, an excruciating order that is difficult to medicate. “Nobody was using virtual reality to reduce patients’ pain before us,” he says. In his VR program, called SnowWorld, Patients who went through the winter scene, throwing snowballs at the penguins, reported that their relief was similar to what they received from intravenous opioids. Brain scans confirmed these findings: virtual reality and opioids resulted in dramatic reductions in neural activity in pain-related areas.
Unlike most medications and surgical procedures, virtual reality has far fewer side effects, mainly nausea and motion sickness. Headphones now cost a fraction of what they once did, and the graphics have significantly improved, resulting in more immersive experiences and fewer potential side effects. Also, says Hoffman, “all major computer companies are pumping billions of dollars into virtual reality as a kind of Internet” – what Mark Zuckerberg called “the Internet embodied” when he announced last fall that Facebook was becoming Meta. A few months later, Microsoft has 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, are that VR therapies, fueled by private sector investment, will rapidly develop into a standard treatment for pain.
On August 8, 2016, Robert Jester, a retired biology teacher at a high school in Greenport, New York, who was moonshine as a chimney sweep – both to support his family and to enjoy the magnificent views – went in a nearby neighborhood for a quick job. The ladder he took was too short, but it felt like a simple sweep, so he decided to get on with the work anyway. He climbed to the top, the ladder slipped and fell to the hard ground below. The pain in his back was so intense that he could not make out rescuers bending over him; he could only see white light.