Neuroscientists at Stanford University have grown a tiny, two-centimeter-long ‘sausage’ made of human cells that may hold answers to one of medicine’s most persistent mysteries: how pain moves through the body — and how to stop it.
Four million cells were coaxed into becoming tiny, brain-like structures called organoids. Then, like parts of a machine, those organoids were linked together to recreate the neural highway that lets us feel the world.
From a pinprick to a warm breeze, every sensation you perceive begins its journey along this ascending sensory pathway. For the first time, scientists have recreated the entire human nervous system’s pain circuit in the lab — from the skin’s nerve endings to the somatosensory cortex of the brain.
This achievement offers an unprecedented way to study not only pain but also touch and movement at the cellular and circuit level, opening a door to potential new therapies for sensory disorders.
“We can now model this pathway non-invasively,” said Dr. Sergiu Pasca, the study’s lead author and a professor of psychiatry and behavioral sciences at Stanford. “The [lab-built circuits] don’t ‘feel’ any pain. They transmit nervous signals that need to be further processed by other centres in our brains for us to experience the unpleasant, aversive feeling of pain.”
Pain on a Plate
The model — called a “sensory assembloid” — is made from human skin cells that scientists reprogrammed into stem cells (known as human-induced pluripotent stem cells). These are then coaxed into forming different parts of the nervous system. Pasca’s team built four organoids. Each represented a major node in the pain pathway: the dorsal root ganglion, spinal cord, thalamus, and somatosensory cortex.
When placed side-by-side, over 100 days, neurons from one cluster grew into another, forming working circuits. By stimulating the first cluster — the one representing sensory neurons in the skin — the scientists triggered a wave of activity that rippled through the entire chain, just like in a living human.
“You’d never have been able to see this wavelike synchrony if you couldn’t watch all four organoids, connected, simultaneously,” said Pasca. “The brain is more than the sum of its parts.”
The pathway they built is formally called the ascending sensory pathway. It’s the main highway for information like touch, heat, and pain. In the body, these signals start at nerve endings in the skin, move to the spinal cord, travel through the thalamus — the brain’s relay center — and finally reach the somatosensory cortex, where we become aware of them.
In essence, the cells built a rudimentary sensory system from scratch.
To test the model, the team used capsaicin — the molecule that gives chili peppers their burn. Just as it does in your mouth, capsaicin triggered a cascade of nervous activity, observable in real time using calcium imaging and electrical recordings.
Not only did the signals move through each node, they also did so with a kind of rhythm. Synchronous patterns emerged, mimicking how real brains process coordinated sensory input. When the researchers compared these connected assembloids to unconnected organoids, the difference was stark. Only the assembled version showed the ripple of activity spanning all four brain regions.
A New Era for Pain Research?
More than 100 million Americans suffer from chronic pain. But the tools to understand and treat it have lagged behind. Animal models often fall short because their pain pathways are different from ours. And ethical limits make it impossible to study human pain circuits directly. This has left researchers largely in the dark about how chronic pain works — and how to reverse it.
“Pain is a huge health problem,” said Dr. Vivianne Tawfik, an anesthesiologist at Stanford who was not involved in the research. “Some 116 million Americans — more than one in three people in the United States — are dealing with chronic pain of one kind or another. I can’t even tell you how sad it is to sit in front of a patient who’s suffering from chronic pain after we’ve tried everything and there’s nothing left in our arsenal.”
Most current treatments were never designed for pain. Antidepressants, anticonvulsants, and especially opioids are used off-label — and often come with serious side effects. That’s why researchers are eager for new options.
One possible target is a protein called Nav1.7, a sodium channel found in sensory neurons. Mutations in the gene SCN9A, which encodes this protein, can make people either hypersensitive to pain or unable to feel it altogether. When Pasca’s team modified the assembloids to include a hypersensitive version of Nav1.7, the system showed more frequent nerve firing. When they blocked it entirely, the transmission of pain signals fell apart — even though the initial neurons still fired.
That suggests pain doesn’t come from one spot firing randomly, but from a synchronized conversation across the entire circuit. It’s just amazing that the researchers were able to model not just cellular defects, but the actual network-level consequences of disease mutations.
From Lab to Clinic?
The assembloids Pasca built are not perfect. They lack brain regions like the amygdala, which help give emotional weight to pain. And they only represent an early stage of development. So, it’s more like a fetal brain than an adult one.
Still, the potential uses are vast. The team is already experimenting with more advanced assembloids that model feedback loops in the brain. They’ve even used them to study genes linked to autism and Tourette’s syndrome.
Pasca, now director of the Stanford Center for Brain Organogenesis, believes that by combining genetics with assembloids, scientists could start to unravel why disorders like autism come with heightened sensitivity to touch, sound, or pain.
With thousands of assembloids possibly produced at scale, drug companies could soon test compounds not just for pain relief, but also for side effects that alter sensory perception. Stanford has already filed a patent on the technology.
The findings appeared in the journal Nature.
