DRUGS TO MAKE THE NOISES STOP
Imagine a noise in your ear that never goes away – like a party in your head that you’re not invited to. For people who suffer tinnitus, this can be a daily reality. A solution could be on the horizon: scientists have managed to prevent tinnitus developing in mice exposed to excessive levels of noise using a drug that’s usually used to treat epilepsy. Tinnitus affects about one in ten adults; for some it can be a truly debilitating condition for which there are few effective treatments, and no known cure. In fact, there are on-going disagreements between some experts about what tinnitus even is. The symptoms vary enormously, from a whisper to a roar, constant to intermittent, temporary to permanent, in one ear, or both. Tinnitus can be triggered by repeated exposure to excessively loud noise, certain prescription drugs, middle ear infections and old age, among other things. The most common trigger is loud noise, which seems to bring about more permanent symptoms than when it is induced by medicines. Researchers have recently begun making sense of some of the biology behind tinnitus. An important process behind noise-induced tinnitus is thought to be
over-activity of cells in a specific part of the brain (called the dorsal cochlea
nucleus (DCN)). Like a rock concert mixing desk, this is the first relay station in the processing pathway from the ears to the brain: it is at the DCN where the auditory nerve, carrying signals from the inner ear, first connects with brain cells. These cells are normally activated in response to real sounds, so the experience of the phantom sounds in tinnitus could be due to over-activity in this region.
A faulty mixing desk Exploring the DCN further, researchers at the University of Pittsburgh School of Medicine looked at molecularsized channels covering the surface of the nerve cells there. These special ‘pores’ (called KCNQ ion channels) transport potassium into and out of brain cells. KCNQ channels normally
have a calming effect on the DCN – inhibiting the activity of the cells there. So the scientists reason that tinnitus could be due to these channels not working normally. And sure enough, the epilepsy drug retigabine, which is already known to increase KCNQ channel activity, prevented tinnitus developing in mice exposed to excessively loud noise. Untreated mice exposed to the noise behaved as though they had tinnitus. Although this study seems to have identified a new process involved in noise-induced tinnitus, it is not the first time a drug has been used to treat the condition. One probable factor involved in tinnitus is overpro
duction of glutamate, a chemical messenger produced by the special ‘ hair’ cells in the inner ear. Glutamate transmits the hairs’ movement
from the inner ear to auditory nerves, where it is converted into electrical impulses that travel to the DCN, and ultimately the brain. Loud noise can cause too much glutamate to be made, and it is this excess that destroys the vital connections between the inner ear and the auditory nerve – an effect known as ‘excitotoxicity’. The connections that regrow to replace those destroyed become overactive, and this is thought to cause tinnitus. Finally! Something that sounds like a cure A paper published in 2007 found that ifenprodil, a drug which blocks certain glutamate receptors, not only prevented noise-induced tinnitus when put directly into the inner ear, but could reverse the
effects, providing it was administered within four days. How these two mechanisms are related (they could be different stages of the same tinnitus for instance, or be due to different types) is not clear, but the team behind the recent study now plan to develop a drug specifically designed for tinnitus. They say such a preventative drug could be useful for soldiers or people who have to work in very noisy conditions. Excitingly, the work may even have implications for other phantom sensations such as the phantom limbs experienced by amputees.