Treating Tinnitus: A potential drug

What is tinnitus? It is a debilitating disorder where people suffer from a chronic "phantom hearing sensation" i.e. perception of sound in the absence of any acoustic stimuli. It is often perceived as hissing or ringing sound in the ears.

Who is at risk? Tinnitus could happen to anyone among us. Even listening to music at high volume for several hours daily is a known cause.

Its prevalence ranges up to 15% in teens and adults. There is an acute increase in its incidence among elderly, workers in noisy environment, or war veterans. Thus, this study assumes great significance.

How does tinnitus progress? The exact changes that lead to its development are still being debated. However, initial abnormal activity in the auditory pathways has been described in most patients. It is also known that trauma to cochlea, an inner ear structure responsible for hearing, can increase the spontaneous activity in central auditory structures located downstream, like inferior colliculus. This central hyperactivity has been suggested as a possible neural basis for tinnitus. This work investigates this hypothesis as a possible mechanism of tinnitus using guinea pigs.

Why use animals? Animals are used to understand the mechanisms underlying a disorder, as well as to develop objective ways of measuring it, and finally evaluate the therapeutic efficacy of any potential drug.

Why choose guinea pigs? Guinea pigs are effective in tinnitus research as it is easy to dissect their ears. Further, they can be induced with tinnitus by exposing them to continuous loud tone for hours while under anaesthesia. Most importantly, they exhibit 'preyer reflex' where they cock their (external) pinnae in response to startling sounds.

How do we know whether an animal is experiencing tinnitus? Since tinnitus causes abnormal hearing perception, it is imperative to employ a behavioural paradigm that enables us to observe the animal and infer its presence. Here the preyer reflex of guinea pigs is exploited for this purpose.

Prepulse inhibition (PPI) is a phenomenon where the preyer reflex is inhibited if a milder pre-stimulus is presented immediately prior to the stronger startle stimulus. This is used to check for normal hearing.

To check for tinnitus, instead of a pre-stimulus a gap is presented in the background noise. If the noise resembled the phantom sound experienced during tinnitus, then animals experiencing tinnitus will fail to detect this gap, possibly due to a 'filling-in'. Thus, a failure to inhibit the startle response confirms existence of tinnitus in an animal that otherwise exhibits PPI.

How close is the guinea pig model of tinnitus? Previously it has been shown using guinea pigs that after a cochlear trauma, hyperactivity in central auditory regions is dependent on stimuli from peripheral auditory structures for certain duration. In later stages, this hyperactivity is generated intrinsically within those central structures without any need for peripheral stimulation. These signs are very similar to those seen in humans. This motivates this study to employ guinea pigs to investigate the effect of the drug furosemide on tinnitus.

For the first time, a study (see reference [1]) provides direct evidence that a drug that reduces spontaneous activity in auditory nerve can relieve tinnitus.

What is furosemide? It is a diuretic i.e. it increases urine production in the kidneys. Though these drugs are typically used in the treatment of heart and renal diseases etc., previously studies in humans have reported that it may reduce tinnitus though only in certain patients.

How does furosemide act? The results presented in this study suggest that an acute administration of furosemide in guinea pigs minimized spontaneous activity in primary auditory areas. This reduced the central hyperactivity that developed post trauma resulting in a decrease in the signs of tinnitus in all animals tested. Importantly, it does not exert its influence on either startle circuitry or the hearing sensitivity. Thus, this study provides a mechanism for effect of furosemide as well as strengthens the central hyperactivity hypothesis.

How good is furosemide as a cure for tinnitus? There are many points to consider before coming to a conclusion. First, the dose of furosemide tested in animals was much higher than the typical dose level used in humans. Since lower doses are suitable for humans, further investigation is required to ascertain its efficacy at lower concentration. Secondly, since this study used a single dose of furosemide, further investigation is needed to check whether the effect is long lasting or requires a repeated administration. Finally, all animals tested were in the first stage of tinnitus. Thus, it is likely that tinnitus becomes resistant to furosemide in the later stages but this needs to be confirmed.

Summary: Furosemide is a promising drug to treat early stages of tinnitus in humans, however many aspects of this drug still needs further investigation.

[1] Mulders, Wilhelmina HAM, Kristin M. Barry, and Donald Robertson. "Effects of Furosemide on Cochlear Neural Activity, Central Hyperactivity and Behavioural Tinnitus after Cochlear Trauma in Guinea Pig." PloS one 9.5 (2014): e97948.