Blocking out the noise: A drug treatment to silence tinnitus?

By Carly Lawler
University of Nottingham, UK

This summary was highly commended by the judges for Access to Understanding 2015

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What is tinnitus?

Have you ever heard a ringing or buzzing in your ears even though there was no sound playing? Most people have. These phantom sounds are often heard following exposure to loud noise, after a night at a party perhaps. For most people it is a fleeting experience that fades quickly. But some people hear these sounds all the time. This is tinnitus, and it can have a severe impact on a person’s quality of life. Tinnitus can disturb sleep, cause anxiety and depression, and interfere with work and social activities.

What causes tinnitus?

We don’t know for sure. In most cases, tinnitus is thought to be related to hearing loss. Exposure to high levels of noise, at work or recreationally, is a common cause of hearing loss. Loud noise can damage the delicate hair cells in the ear, which reduces sensitivity to sound. Unexpectedly, this can lead to increased activity in parts of the brain that process sounds. This ‘hyperactivity’ in the brain may be a cause of tinnitus.

Hyperactivity: Two distinct stages

Researchers from the University of Western Australia previously showed that, following noise-induced damage to the ear, hyperactivity in the brain develops in two stages. In the first stage, hyperactivity is driven by signals being sent from the ear to the brain. These signals occur spontaneously, even when there is no sound to generate them. In the second stage, hyperactivity becomes self-sustaining, no longer depending on these spontaneous signals from the ear. This led the researchers to ask: If we could reduce the spontaneous signals during the first stage, could we block out hyperactivity and tinnitus?

How might furosemide help?

The drug furosemide is commonly used to treat high blood pressure, although early tests have suggested that it could also reduce tinnitus. Furosemide is known to weaken the spontaneous signals sent from the ear to the brain. Furosemide may therefore be well placed to target hyperactivity during the first stage. If delivered soon after noise-induced damage to the ear, it could reduce hyperactivity and tinnitus. The researchers tested this in the guinea pig. This allowed them to monitor behavioural signs of tinnitus, spontaneous signals sent from the ear to the brain, and hyperactivity in the brain.

Guinea pigs with tinnitus?

The researchers exposed guinea pigs to a loud noise and then monitored them weekly to see if they developed signs of tinnitus. To tell if a guinea pig had tinnitus, the researchers used a test that measures how startled the animal is by a sudden sound. This startle sound is preceded by a quieter sound, which sometimes contains a gap. The gap provides a warning that the startle sound is coming, and so the animal startles less. However, animals with tinnitus aren’t able to detect the gap, and so they startle equally whether or not the gap is present.

Just under half of the guinea pigs developed signs of tinnitus. The researchers gave some of these animals a dose of furosemide, which they hoped would reduce tinnitus. They gave the others a salt solution, which they did not expect to have any effect on tinnitus. One hour after receiving furosemide or salt solution, the animals were tested again.

Did furosemide work?

It did. Furosemide reduced the early signs of tinnitus in all of the guinea pigs that received this treatment. In contrast, none of the animals that received the salt solution showed any improvement. This finding provides important evidence that furosemide can reduce tinnitus that develops soon after noise-induced damage to the ear.

To determine how furosemide worked, the researchers exposed another group of guinea pigs to the same loud noise. They made measurements on these animals before and after treatment with furosemide. Furosemide reduced the spontaneous signals being sent from the ear to the brain, and eliminated hyperactivity in the brain. This supports the idea that hyperactivity could have caused the tinnitus that the guinea pigs experienced.

Could furosemide work in humans?

This research shows that treatment with furosemide following loud noise exposure can reduce signs of tinnitus in animals. But could it do the same in humans? What remains unclear is the dosage needed to safely bring about the same effect in humans, and whether the benefits could be sustained over the long term. We also need to understand how soon after loud noise exposure furosemide must be delivered in order to be effective.

Tinnitus is a common complaint among people who are exposed to intense noise, members of the armed forces returning from service, for example. This research offers hope that a drug treatment delivered soon after noise exposure could silence tinnitus.

This article describes the research published in:

Effects of furosemide on cochlear neural activity, central hyperactivity and behavioural tinnitus after cochlear trauma in guinea pig
H. A. M. Mulders , K. M. Barry, D. Robertson PLoS One (2014) 9(5), e97948

This article was selected for inclusion in the competition by Action on Hearing Loss.



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