Scientists Grow Complete Nerve Circuit to Send Pain to Brain for the First Time – Tested with Hot Peppers

US researchers have reported the first laboratory reconstruction of the entire pain pathway, from the nerve endings in the skin to the brain. The work could help develop painkillers that could replace addictive opiates. The “test tube brain” could also help study a host of other nervous system diseases, ensuring ethically sound research without humans or animals.

Image source: AI generation Grok 3/3DNews

Scientists from Stanford University in California have managed to recreate nervous tissue in all its relative diversity and establish connections between its elements. The research is being conducted by a group led by Romanian neurobiologist Sergiu P. Pașca. It was he who introduced the concept of assembloids back in 2017 — complex three-dimensional cell models created in the laboratory. Assembloids are a combination of two or more organelles — spherical cellular structures or cultured cells combined to reproduce the structural and functional properties of an organ.

Pashka’s group derived induced stem cells from human skin cells, which were then stimulated to form four types of neural tissue: from sensory neurons in the skin to conductive neural tissue and, finally, to the tissue of the cerebral cortex. The scientists did not reproduce (and probably could not reproduce) the secondary neural signal circuit responsible for interpreting sensations in the brain, particularly pain. Moreover, this would be unethical. Assembloids do not feel pain and can be used for the most “horrible” experiments in modeling the human nervous system.

Image source: Nature 2025

All four organoids were placed in a culture dish, where they fused to form a continuous neural circuit from end to end. This took about 100 days, resulting in an assembloid nearly 1 cm long containing about 4 million cells. Neural connections linked the component organoids, and patterns of synchronous signaling emerged in the system.

The pain signal was triggered by a drop of capsaicin, the substance that makes peppers hot. After its introduction, wave-like neuroimpulse signals began to be recorded, spreading from the site of excitation to the end point, simulating the brain.

Nervous circuit assembloid under an electron microscope

«”You would never be able to see this wave-like synchrony if you couldn’t observe all four organelles at once,” Pashka said. “The brain is more than the sum of its parts.”

The university has also filed a patent related to the discovery, but has not yet decided how to commercialize it.