RNID is funding a project at King’s College London and the University of Nottingham to test if it is possible to lessen or even silence tinnitus, by blocking the activity of an ion channel associated with chronic pain.
Tinnitus is the perception of sound in the absence of an external source, usually experienced as a ringing or buzzing in the ears. Approximately 10-15% of the population suffers from chronic tinnitus (Globe Life Sciences, 2019); it is a common and distressing condition for which there is currently no effective treatment. Tinnitus can lead to problems with sleeping and concentration, and is linked to both anxiety and depression.
There are a wide range of factors that can damage the auditory system and trigger tinnitus, including exposure to loud noise or ototoxic (“ear-toxic”) drugs, or head injury. Although the underlying biological processes and drivers of tinnitus are still not completely clear, scientists believe that tinnitus is associated with changes to the auditory system, which in turn cause increased activity in the hearing brain and the consequent perception of a phantom sound.
Neuropathic pain is a type of chronic pain where patients experience shooting or burning pains without there being an external reason for the pain. As with tinnitus, it appears to be a result of increased activity in the nervous system, causing continuous activation of pain-sensitive nerve fibres. Patients with neuropathic pain experience persistent, phantom pain sensations, just like tinnitus patients experience persistent, phantom sound perceptions.
Several studies have shown that there are similarities between the biological processes involved in chronic pain and tinnitus. So we’re funding a project to look more closely at these similarities, and explore whether approaches to treating chronic pain may also help to treat tinnitus.
Testing if treatments for chronic pain can silence tinnitus
Professor Peter McNaughton’s team, based at King’s College London, has identified that a type of ion channel, called HCN2, is responsible for driving neuropathic pain. Ion channels are proteins that span the surface membrane of electrically-active cells like nerve cells and allow charged particles (such as sodium or potassium ions) to pass in and out of cells – without these channels, ions cannot move across the cell’s surface.
Professor McNaughton’s team have shown that when ions flow through the HCN2 channels, they trigger the activation of pain-sensitive nerve fibres, creating a constant sensation of pain. When the researchers blocked these ion channels in mice, they were able to eliminate pain in a mouse model of chronic pain (Emery, E et al (2011) Science).
HCN2 channels are also found in the nerve fibres of the auditory system, which carry information from the ear to the brain. These fibres are often damaged after exposure to loud noise, which can lead to tinnitus. Some preliminary studies carried out by the King’s College London team have shown that blocking HCN2 channels with selective drugs significantly reduces tinnitus in animal models.
The researchers now want to study the role of HCN2 channels in tinnitus in more detail. Professor McNaughton’s team, working with experts in tinnitus at the University of Nottingham, will test the effectiveness of different drugs that block HCN2 channels in reducing tinnitus in animals. This work is being supported by one of our Translational Research Grants.
Why this project is important
We have only a limited understanding of the biological processes and molecular drivers that underlie tinnitus – this is one reason why there are currently no effective treatments. It is vital that we discover more processes and molecules that can be targeted with drugs to silence tinnitus. This project is looking at a new approach to treating tinnitus, and could ultimately lead to the development of new, effective treatments.
King’s College London is collaborating with MSD (tradename of Merck & Co., Inc., Kenilworth, NJ, USA) for the development of compounds that inhibit HCN2 under an exclusive research agreement.