Allan Basbaum has spent 50 years searching the nervous system for the places where pain begins – and where it can be stopped

by Stephani Sutherland  BIO

Detail from Composition with Red, Blue and Yellow (1930, full image below) by Piet Mondrian. Courtesy Zurich Art Gallery/Wikipedia

is a neuroscientist and science communicator covering pain and health research. She lives in California, US.

Edited byPam Weintraub

One night in 2000, Allan Basbaum was at the Pierre Hotel on Central Park, wearing a tuxedo after presenting a neuroscience award to one of his colleagues before a roomful of scientists, Nobel laureates among them. His wife, Carol, a cancer biologist, had accompanied him from San Francisco, where they both ran laboratories at the University of California. Late that night, he was struck by agonising stomach pain. Alarmed, they went to the emergency room at Lenox Hill Hospital, where the waiting area was jammed and hours passed before anyone could see him.

‘So I’m out in the waiting room; I’m periodically screaming,’ Basbaum says. After two hours, Carol went to the bathroom, leaving him alone. Finally, a man came over and began speaking to him, gently prodding him. ‘He checks my pulse, he asks: “Does this hurt?”’ Basbaum says. As the man attended to him, ‘the pain really started to get much better,’ and Basbaum relaxed. When Carol returned, he told her about the long-awaited treatment. ‘She says: “Allan, he’s one of the patients. He’s been doing that to everybody here.” But finally, someone was taking care of me.’ And that brought relief.

By then, Basbaum had spent three decades studying the physiology of pain, mapping the neural circuits that carry signals from the body toward the brain. He wanted to understand how those signals become pain. His experience brought to life the questions he’d been marvelling at for years: how do fear, context and expectation shape the body’s most urgent alarm? How do placebos work? And how could someone relieve his pain, just by paying attention?

Basbaum understood the Gordian knot at the heart of pain: the brain could influence pain before a person consciously felt it. His work over the past 50 years has been to untangle that loop, following signals through the spinal cord to the brain and back again.

Composition with Red, Blue and Yellow (1930) by Piet Mondrian. Courtesy Zurich Art Gallery/Wikipedia

Basbaum likens pain to the experience of beauty. Take Piet Mondrian. One person sees a painting of coloured bars and squares, and thinks: I could do that. Another, steeped in the history and meaning of the work, is moved to tears. The image on the retina may be much the same; the experience is not. Pain, Basbaum argues, works in a similar way. There is no such thing as an inherently painful stimulus, only stimuli that, in most people, under most conditions, will produce pain.

A truly subjective experience, pain can seem ephemeral. Yet, like all bodily sensations, it arises from the interactions of molecules and cells. At age 78, still at the University of California, San Francisco (UCSF) leading one of the nation’s most prolific pain research groups, Basbaum’s aim remains unchanged: unravel the signal to find ways of treating pain.

The brain is not where Basbaum wants treatment to begin. ‘My bias is to understand how the information gets to the brain and look for places along the way, preferably way out in the periphery, that I think are important drivers to initiate the whole process,’ he says. ‘By interfering with those drivers, we can disrupt chronic pain altogether.’

Nerve-cutting procedures didn’t produce lasting relief, and patients reported that pain could return worse than before

The history of pain research goes back centuries. René Descartes, who declared a split between body and mind, placed pain in the physical realm. His Treatise of Man (1662) included a famous illustration: a fire burns a boy’s foot, its heat activating a withdrawal reflex through a tube-like structure to the brain. However crude, that model helped lay the foundation for modern sensory physiology.

From René Descartes’s Treatise on Man (1662). Courtesy Wikipedia

Two centuries later, Johannes Müller refined that model. Sensory information reached the brain through nerves, he argued, with each sense travelling along its own neural system. Pain was grouped with touch, heat, cold, itching and pleasure in the body’s broad field of feeling.

By 1894, Max von Frey had divvied bodily feeling into four parts: mechanical touch, warmth, cold and pain, each carried by distinct nerve types. Pain, he added, was contained within its own system, its signals travelling to discrete pain centres in the brain.

Around this time, researchers drew a distinction between the complex experience of pain and ‘nociception’, the sensory response to a noxious or harmful stimulus. That distinction, coined by Sir Charles Sherrington, remains a core principle of pain research today. Nociception occurs in the body, in the nerves and the spinal cord. Pain requires the brain.

These complexities undermined the old notion of a single pain pathway. Historically, the idea was simple: injury sent pain input like a telephone wire to the brain. ‘You want to get rid of it? Poof – you just cut it,’ Basbaum says. But nerve-cutting procedures didn’t produce lasting relief, and patients reported that pain could return worse than before. Nor did injury and pain always correspond. Field surgeons in the United States Civil War reported that amputees felt excruciating phantom pain in limbs no longer there; soldiers with severe wounds sometimes felt little pain at all. These phenomena pointed to a system much more complex than a telephone wire from body to brain.

Even so, sensory communication did travel electrically. By the mid-20th century, Alan Hodgkin and Andrew Huxley had worked out the action potential, the bioelectrical pulse by which neurons communicate, and researchers had begun tracing the anatomy of sensation from body to brain. Sensory neurons live in clusters called dorsal root ganglia just outside the spinal cord. Each has an unusual architecture: one long, thin axon – a nerve fibre that carries electrical signals – extends out to the body, while a shorter branch reaches into the spinal cord. Large cells with insulated axons carry fast-moving touch signals; smaller, slower-conducting cells with bare axons relay temperature and pain. But details beyond that were sketchy.

By that time, pain was a matter of fierce dispute. That’s when the Canadian psychologist Ronald Melzack and the British neuroscientist Patrick Wall – the two men who would become Basbaum’s mentors – teamed up to tackle the problem. In a 1962 publication, Melzack and Wall boiled down the controversy to two prevailing theories.

The first, ‘specificity theory’, held that pain occupied its own system: pain sensors in the skin relayed information through pain nerves to pain centres in the brain. But that model was too rigid. It could not explain why pain varied so much with context, expectation or injury.

The newer alternative was ‘pattern theory’, which held that pain did not travel along its own dedicated pathway. Instead, sensations depended on how many nerves fired, how fast they fired and........

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