The Oxford Science Lecture Series

Professor Irene Tracey, FRS

University of Oxford

"Seeing Pain: A Window on the Human Brain through Neuroimaging" 

Dorothy Hodgkin Memorial Lecture 2024

Somerville College, Oxford, 8th March 2024

Professor Irene Tracey is the Vice-Chancellor of the University of Oxford and Professor of Anaesthetic Neuroscience at the Nuffield Department of Clinical Neurosciences. She grew up in Oxford, attending school in Kidlington and then studying Biochemistry at Merton College. She did her DPhil in Oxford and then spent time at Harvard Medical School before returning to Oxford where she helped to found the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain.

Professor Tracey was introduced by the Principal of Somerville who added that 2024 marks 30 years since the death of Dorothy Hodgkin (1910 - 1994) and 60 years since she received the Nobel Prize in Chemistry (1964). The College and Oxford AWiSE had assembled a display of medals, including her Nobel Prize medal, photographs, a bust of Dorothy and other memorabilia from Dorothy’s time in Oxford. The Principal praised Professor Tracey for her brilliant first year as Vice-Chancellor, commenting that she understood research, the University and the city of Oxford.

Professor Tracey began her lecture by describing the technique of x-ray crystallography which was developed by William Bragg. As it was International Women’s Day, she flagged up that he had eleven women in his research team of eighteen which was remarkable for the early days of the 20th century. One of his students, Kathleen Lonsdale, built some of her x-ray crystallography equipment from household items including food and drink tins! She went on to be Dorothy Hodgkin’s supervisor.

Professor Tracey explained that the brain contains neurons, which are the cells that do the computation in the brain, and which are connected by white matter. Glial cells in the brain control the blood flow and feed the neurons. There are no nerves in the brain which is why it is possible to do surgery in the brain while the patient is conscious, so that the surgeon can ensure no vital areas are damaged.

Beginning with work by the Greek anatomist, Galen, in the second century and moving through Leonardo da Vinci and Descartes in the sixteenth century, Professor Tracey gave a brief history of research on the brain. She highlighted the work of Oxford scientists Thomas Willis, and Sir Charles Scott Sherrington who realised that the brain is a highly perfused organ. 

When an area of the brain is active it needs extra blood delivered to it to supply oxygen and glucose. This is the basis of how functional magnetic resonance imaging (fMRI) of the brain works. Oxygen is carried to the brain by haemoglobin which contains iron which is paramagnetic until oxygen is bound to it when it becomes diamagnetic. Paramagnetic iron interacts with the magnetic field within the MRI scanner so when the iron delivers the oxygen to the active neurons, this distorts the magnetic field in that region of the brain and can be detected in the MR image. This technique was pioneered by Sir George Radda, who was Professor Tracey’s supervisor in Oxford, and then developed in Massachusetts General Hospital. When Professor Tracey returned to Oxford, she set up her lab to explore the areas of the brain which are activated when we feel pain.

Acute pain is a warning system, where the brain tells you that something is wrong and that you need to do something about it. Chronic pain is different, it is the dark side of pain and is an indication that your system is going wrong. It is now gradually being recognised as a disease of its own. Professor Tracey researches the transmission of pain from the nerves in the skin to areas of the brain. She said that pain is subjective, you don’t know how your experience compares to that of another person, and this has made it difficult to study and treat. With the development of fMRI it is now possible to ‘put a number’ on the level of pain and she explores this by inflicting pain on her test subjects and then measuring the level of activation in the brain. She has shown that your mood and your attention to the injury can affect how you feel pain and that if you distract someone they experience less pain than if they are concentrating on it or are anxious.

Professor Tracey has identified signals in the brain stem, the area of the brain that communicates signals from the spinal cord. She calls these the ‘good cop’ and ‘bad cop’ and explained that the good cop is what helps you overcome acute pain whereas the bad cop is connected with chronic pain. It is implicated in the continuation of pain after the cause has gone, such as after a hip replacement. If we can learn more about it then hopefully we can develop drugs to combat it. The good cop is also involved in the placebo effect which fMRI has shown to cause changes in the signals in the brain. Professor Tracey took a group of volunteers and explained that she would inflict pain and measure the signals in the brain with and without administration of pain-relieving opiates. In this experiment they started the drug without telling the volunteer and they saw a decrease in the perceived experience and the signal in the brain. Keeping the dose constant they then told the volunteer they were starting the drug and both the perceived experience and the signal in the brain dropped further. So the expectation of an improvement actually caused a physical change. Finally, they told the volunteer bad news, that they were stopping the drug, but in fact they maintained the infusion. In this case, the signal in the brain went back to the level it was when the drug was first infused but the perceived experience went back to the baseline level when no drug had been given. This is the effect of the ‘bad cop’ being activated by anxiety and increasing the experience of pain. Professor Tracey commented that it is important for clinicians to understand the effect of their words when they are explaining a course of treatment, the way they tell a patient can be interpreted differently, depending on whether the patient is optimistic or pessimistic and this can affect their experience of pain.

Professor Tracey described a revolutionary study in Oxford into the effect of a surgery on the experience of pain. Surgeons had been performing a surgery to remove a small piece of bone to relieve shoulder pain. After many years of application to get ethical approval, they received permission to perform a placebo-controlled surgical trial. They performed the surgery on a group of patients but only removed the piece of bone from some of them. There was no difference in the effect seen between the two surgical groups. They concluded that the difference between the surgical groups and those receiving no treatment might be the result of a placebo effect or post-operative physiotherapy but was not due to the removal of a piece of bone!

Finally, as she was running out of time, Professor Tracey whizzed through slides showing a system they have developed to give anaesthetists more information about the level of consciousness of patients under anaesthesia, with the aim of reducing the level of anaesthesia needed for surgery.

The evening concluded with formal questions in the hall and over drinks. The full lecture is available on YouTube: Dorothy Hodgkin Memorial Lecture 2024 (youtube.com)

Prof. Carolyn Carr

Associate Professor of Biomedical Science

University of Oxford