Treatments for Tinnitus: An Overview of Future Possibilities

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Introduction
I would like to provide an overview of some prospective future treatments for tinnitus based on current research into its mechanisms. The present list will only include treatments aimed at reducing or eliminating the tinnitus signal itself, rather than at facilitating long-term habituation to tinnitus (as in Tinnitus Retraining Therapy), or at facilitating coping (as in masking, cognitive psychological yherapy and biofeedback). Aside from the options presented below, stem-cell research may offer a further option for such treatment if it becomes possible to regrow damaged hair cells, but this treatment is in my view a long way off and may well fail to address the apparent central component of much persistent tinnitus. Cochlear neurectomy, another proposed treatment, certainly fails to address such a central component.
A. Treatments for Acute Tinnitus aimed at preventing its establishment as Chronic Tinnitus
A1. Drug therapy for acute hearing loss
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The US Navy is apparently developing a pill which can reverse hearing damage within a 5-week window which they are confident of completing within 5 years. The technique uses micro-devices or micro-catheters inserted in the ear to deliver antioxidant pharmaceuticals that protect hair cells from damage by free oxygen radicals following sound exposure. --A report on this treatment is available on HearNet at www.hearnet.com/features/articles/artist_article_navy.shtml.
see also the discussion of drug treatments for acute vs. chronic tinnitus in the thread glutamate antagonists.
A. Anti-reorganisational Drugs
If cortical reorganisation does have a causative role in chronic tinnitus - as suggested by the Edge-Frequency Cortical Reorganisation hypothesis (EFCR-H) described in section B - then certain drugs may prevent chronic tinnitus from occurring. These drugs would be similar to those which are given to surgery patients before or after amputation of a limb; such drugs block the brain receptors involved in reorganisation and thus prevent the brain changes which produce and sustain phantom pain. --This thinking is based on Herta Flors tinnitus research; see the BBC link given under section B.
B. Treatments aimed at reducing or eliminating Chronic Tinnitus
These treatments are categorised according to which causative factor in tinnitus they are designed to treat. Two categories are distinguished - treatments which address the hyperactivity of central auditory structures which may represent the tinnitus signal, and treatments which address the cortical reorganisation which may lead to and maintain tinnitus. Note that it is possible that these two different models of tinnitus are not necessarily distinct from each other; central hyperactivity may be cause by cortical reorganisation and vice-versa. As such, treatments from both the B1 and the B categories may eventually become possible, and may even be presented as alternatives to a single patient.
B1. Treatments based on the Dorsal Chochlear Nucleus Disinhibition hypothesis (DCND-H)
Both acute and chronic tinnitus subjects show hyperactivity in a region of the brain called the dorsal cochlear nucleus (DCN), presumably resulting from a loss of inhibition of activity which has been shown to result from hair cell damage. If this hyperactivity has a causative and maintaining effect in chronic tinnitus, then the following treatments may be effective. --This model of tinnitus is discussed in Dr. James Kaltenbachs 00 ATA speech at www.ata.org/home/kaltenbach.html and in several of the abstracts posted in the Mechanisms of Tinnitus thread. Some reservations about this model and its application to bilateral (both ears) and non-somatic tinnitus are expressed in pages 1- of Richard Levines Somatic Tinnitus paper at epl.meei.harvard.edu/~ral/SomaticTinnPaper.pdf.
(N.B. Modified versions of the treatments listed under sections B1a and B1b could presumably be used on other central auditory structures, such as the inferior colliculus (IC), if these prove more important than the DCN in chronic tinnitus).
B1a. Restoration of DCN Inhibition through Electrical Stimulation
Electrical stimulation of the auditory nerve which leads from the ear to the DCN, or stimulation of the DCN itself, has been shown to suppress tinnitus. This is evident in about 60% of tinnitus sufferers who receive cochlear implants or auditory brainstem implants, who find that the electrical current of these implants reduces their tinnitus while the implant is installed. However, an alternative pathway of electrical stimluation would be necessary for many patients, as the electrical stimulation ofthe inner ear by a cochlear implant kills any remaining hair cells. --This treatment possibility is referred to in pages 0-1 of the Levine paper (see the link under section B1), in a survey of tinnitus at www.utmb.edu/otoref/Grnds/Tinnitus-01/tinnitus-01.html, and in page of the Kaltenbach speech (see link in B1).
B1b. Restoration of DCN Inhibition through Drug Therapy
One of the most important inhibitory neurotransmitters in the body is GABA. If a drug which mimics the effects of (or stimulates the action of) GABA or other inhibitory neurotransmitters can be found, it may reduce hyperactivity in the DCN or inferior colliculus (IC). Drug trials so far have proved inconclusive; the effectiveness of the GABA-agonist alprazolam (Xanax) in reducing tinnitus is unclear, and the drug baclofen (Lioresal), which does mimic the action of GABA, appears no more effective than a placebo; anti-convulsants have proved likewise inconsistent; intravenous lidocaine (= lignocaine, xylocaine) often reduces tinnitus, but can make high-pitched tinnitus worse and induces excessive side effects. Most problematically, because substances like GABA are active throughout much of the human body, a form of the drug or of its administration would have to be found which could locally target the DCN or IC. --This treatment possibility is referred to in the Kaltenbach speech (see link in B1); a disappointing baclofen trial is discussed as part of a New Scientist article reproduced on alt.support.tinnitus at groups.google.com/groups?selm=hbAerBA18w0EwtY%40woolner.demon.co.ukoe=UTF-8output=gplain.
B1c. Reduction of DCN Output
The output of a hyperactive DCN could be reduced or abolished, thereby preventing this output from reaching the more central regions of the auditory brain which convert such signals into perceptions. The output could be reduced by lesioning the DCN or by transecting its output tracts. Despite the apparent destructiveness of these procedures, severing of the DCN output tracts appears to have little impact on the hearing of test animals. --These treatment options are discussed in pages 0-1 of the Levine paper, though Levines results are specific to lateralised (one-sided) and somatic (rather than otic, or ear-induced) tinnitus.
B. Treatments based on the Edge-Frequency Cortical Reorganisation hypothesis (EFCR-H)
Chronic tinnitus may result from cortical reorganisation following damage to hair cells, in much the same way as phatom pain results from cortical reorganisation following the loss of a limb. Tinnitus subjects demonstrate cortical reorganisation patterns in which the area of the brain corresponding to the frequency region of the tinnitus signal is expanded; a reverse reoganisation is seen in phantom pain patients, for whom the area of the brain corresponding to the amputated limb is often reduced. It is believed that cortical reorganisation in tinnitus results because the brain rewires itself to receive input from the functional hair cells adjacent to damaged hair cells in the cochlea; the resulting imbalanced signal may produce tinnitus, perhaps by causing hyperactivity in central auditory structures such as the DCN. It remains unclear whether cortical reorganisation causes and maintains tinnitus, or whether it shares a common cause or in fact results from the tinnitus signal. --A paper contributing to this theory from Dr. Herta Flor and her associates is available at www.clinical-psychology.uni-konstanz.de/stuff/ abstracts/Muhlnickel_et_al_PNAS_8.pdf; popularised details of Flors work are found at Natures Science Update www.nature.com/nsu/8080/8080-4.html. It is worth noting that Flors studies have been limited to patients with tonal, as opposed to noisiform, tinnitus.
Treatments based on this aspect of the tinnitus mechanism aim to reverse cortical reorganisation by applying certain sounds to the brain. One such treatment is the UltraQuiet therapy proposed by Dr. Martin Lenhardt, which I criticised early in the Treatments for Tinnitus thread in large part because the ultrasound frequencies used for therapeutic effect do not seem sufficiently targeted to the patients individual tinnitus - and as such any benefit is likely to be in no way different from that offered by conventional masking, except in the case of patients who are too deaf to benefit from conventional masking.
More promising, and less well-publicised, is Dr. Herta Flors work at re-tuning the brain by having the tinnitus patient process sounds close to, but not matching, his or her tinnitus frequency. This treatment is based on phantom limb pain patients who underwent exercises in which they identified the location of electric stimuli applied to their stumps, thus promoting an increase in the size of the shrunken brain area corresponding to the lost limb; these patients have experienced a 70% reduction in phantom pain. Having tinnitus patients discriminate between different pairs of tones pitched at frequencies near to their tinnitus frequency may increase the areas of the brain corresponding to these frequencies, and thus decrease the enlarged area of the brain corresponding to the tinnitus frequency. The tinnitus patients in Flors preliminary trial reported a 5% reduction in tinnitus from this treatment; none of the control patients - who heard tones unrelated to their tinnitus - experienced benefit. However, as all of Flors work on cortical reorganisation has been limited to patients with tonal tinnitus, it is unclear whether the EFCR-H or the proposed treatment would apply to patients with non-tonal tinnitus. --Details of this treatment possibility are found in another account of Flors work, through the BBC health news website at news.bbc.co.uk/1/hi/health/188741.stm.
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