Oxford engineers to develop advanced human models of pain

Chronic pain affects more than one in five adults worldwide, causing widespread suffering and placing a major burden on healthcare systems. Despite its prevalence, effective treatments remain limited, largely because current animal and laboratory models cannot fully replicate the complex biological processes that drive pain in humans. Advances in stem cell science, tissue engineering, and computational biology are now opening the door to next-generation human models that more accurately reflect pain mechanisms, offering new hope for developing safer, more effective therapies.

The project focuses on the sensory pain pathways that underpin many chronic pain conditions, developing scalable and disease-relevant human models that capture the complex biological interactions driving pain. Professor Cathy Ye from Engineering Science and Professor Zameel Cader from Oxford’s Nuffield Department of Clinical Neurosciences will concentrate on two major conditions, osteoarthritis pain, caused by joint degeneration, and neuropathic pain, resulting from nerve injury, to ensure real-world relevance.

This project takes an innovative, interdisciplinary approach that combines engineering, stem cell science, and clinical insight to create realistic human models of pain. With clear milestones, robust validation, and access to world-class facilities, the project is designed to be both feasible and impactful. This framework will accelerate translation into real-world applications and set new standards for developing and adopting human-relevant models in pain research.

Using cutting-edge stem cell technologies, 3D tissue engineering, and AI-driven analysis, the team will create advanced in vitro systems that can test new treatments, reveal drug targets, and provide insights into how individual patients respond to pain therapies.

Professor Cathy Ye and her group in Engineering Science will lead the bioengineering side of the project, responsible for creating three-dimensional tissue models that mimic the structure and function of human joints. The team will begin by developing simplified cartilage models, which will later be expanded to include bone and nerve components. These engineered tissues will provide the foundation for the wider project team to explore the mechanisms of chronic pain and validate findings against clinical data.

The group will design and fabricate biomaterials that best replicate natural tissue microenvironments, using bioreactors to sustain and control growth outside the human body.

This research will provide powerful new tools for studying pain biology, deepening the understanding of how nerve, vascular, and immune systems interact in chronic pain. By providing the optimal environment, including biomaterials and bioreactors, for the cells to form tissues outside the human body, they will be able to develop innovative human models that better replicate complex pain pathways. This research has wide-ranging applications that could transform chronic pain treatment and research. Pharmaceutical companies will be able to use these models to test new pain medications in a system that better reflects human biology, increasing the chances of successful clinical trials.

Professor Cader says “Our goal is to bring human biology to the core of pain research. By recreating the cellular environments where pain originates, we can uncover new mechanisms and improve drug discovery. An important aspect of this new programme is to bring our learning and tools to the pain research community, which ultimately, we hope will lead to treatments that will work”.

Prof Ye said: ‘‘I am really excited to be part of this interdisciplinary team to provide a more effective alternative to animal models. This project supports efforts to replace animal testing in medical research. By linking human in vitro models to patient clinical features, the research will help identify why some individuals respond differently to pain medications, paving the way for tailored treatments.’’

A joint £15.9 million investment by the UKRI Medical Research Council (MRC), Wellcome and UKRI Innovate UK will enable the development of advanced, specific and highly reproducible human in vitro models with the aim of making them widely available to researchers in academia and industry.