STOP-TRANSIT study: Peri-procedural targets in toothache to stop transition to phantom neuropathic tooth pain
This research aims to allow the development of new therapeutics for orofacial pain patients.
Toothache is common, affecting up to 1 in 10 people in the UK and 1 in 3 worldwide. Treatment involves either removing the tooth (extraction) or removing the nerve inside the tooth (root-canal therapy). In the UK last year nearly 5 million of these treatments were carried out. Both these treatments involve intentionally removing the tooth’s nerve supply, which causes no problems in the majority of cases, but in a small number (~2%) pain continues despite the treatment.
This pain is real but is colloquially known as “phantom” tooth pain as the nerve supply has been removed. As the pain is life-long it significantly affects sufferers’ quality-of-life as, in essence, it is like living with toothache every day of the week. As our ageing population expands it is likely that we will see increasing amounts of phantom tooth pain arising. This is because, as national surveys demonstrate, we are keeping our teeth for longer (the over-55s have 19 teeth on average), and also because as we age our nervous system is less able to adapt and heal from treatments such as root canal therapy and extraction.
We propose to develop a model to mimic a tooth and its nerve supply using cells in the laboratory. “Toothache” will then be started in the model using chemicals from bacteria that cause tooth decay, and the toothache would be tested with a variety of chemical messengers used by our nerves and body to encourage it to change into phantom tooth pain. We will then compare how the model works with nerve supplies taken from recently extracted healthy human teeth (for the purposes of straightening teeth) to confirm it acts in a similar way. Finally, the model will be used to help us to develop treatments to stop the change to phantom tooth pain. In the future, the model will also help reduce the need for animal testing and speed up the process of other dental treatments becoming available to patients.
- Differentiation of pulp stem cells into neurones and odontoblasts and confirmation they act as cells in vivo.
- Confirm that stem cell derived neurones and odontoblasts act as one tissue when grown together in 2D.
- Collection of tooth samples from September 2019 to ensure adequate number of explants. 3D model and explants subject to bacterial endotoxins and neuropeptides. Confirm equivalence of response with immunohistochemistry. Test 3D model with known IDO antagonist.