ArticlePDF Available
Zoa A. Dziuganowska (2016) Tinnitus - Characteristics and Therapy. Int J Bioorg Chem Mol Biol. 4(2), 17-23.
17
OPEN ACCESS http://scidoc.org/IJBCMB.php
International Journal of Bioorganic Chemistry & Molecular Biology (IJBCMB)
ISSN 2332-2756
Tinnitus - Characteristics and Therapy
Review Article
Zoa A. Dziuganowska
Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wybrzeże Wyspiańskiego, Wrocław, Poland.
Tinnitus from Historical Perspective
The origin of a name of a disorder derives from the Latin
word “tinnire that means to ring” and in this context is dened
as ringing in the ear”. Tinnitus-on the contrary to the common
opinion-is the disorder known from the Antiquity. According to
some authors [1], the rst reference to tinnitus can be found in
the Ebers Papyrus dated back to the 17th Egyptian dynasty (1650-
1532 B.C.) where it was dened as ‘bewitched ear’. Tinnitus was
not always treated as disease: ancient Indians recognized it as a
sign of communion with space reserved only to spiritual elite;
ancient Egyptians as a gift for divination; other civilizations
considered it as Titus’s curse-one of the most severe mythical
punishments put on humanity [2]. The rst undisputed reference
to tinnitus was found in Corpus Hippocraticum where it was claimed
that symptom is connected with hearing loss, headache and
menstruation disorders.
These annotations did not only concern the description of the
disease but also methods of its treatment. Three methods were
used: fumigation involving a variety of substances deriving from
trees, herbs, sometimes even animal materials (bones or horns);
insertion of wool treated with various materials into ears; direct
administration of drugs to ear via a bronze tube [3]. Various
materials such as honey, vinegar, rose oils, laurel oil etc. were
applied. Galen (130-200 A.D.) used, as the rst, sedatives like
opium or mandrake juice in order to dull the brain’s response to
tinnitus. Therapy of tinnitus changed in the Renaissance when
Paracelsus introduced rst mineral-based drugs. Later, the more
advanced techniques such as surgeries (beginning of 17th century),
electric stimulations (second half of 18th century) or acoustic
stimulation (middle of 19th century) were developed.
Characteristics of Tinnitus
Denition and Description
Tinnitus is dened as phantom auditory perception [4]. This broad
denition includes the auditory hallucinations of schizophrenia,
a variety of somatosounds such as palatal myoclonus, abnormal
opening or patency of the Eustachian tube, temporomandibular
joint disease, spontaneous otoacoustic emissions and sounds of
vascular origin as well as sensation resulting from a malfunction
of the cochlea or auditory nerve. Tinnitus can be classied as
objective or subjective. Objective tinnitus can be heard by an
observer and, what is more, it can be measured by means of
appropriate equipment. Subjective tinnitus is heard only by the
sufferer. Nowadays, objective tinnitus is treated as somatosounds.
Abstract
Many papers have been published so far that the need for an updated review prompted the author to write this article and
to describe historical perspective, characteristics, epidemiology, causes, pathophysiology, and treatments of tinnitus. Despite
of the common opinion, this one of the most annoying of ear disorders, has been known from the Antiquity. Nowadays,
it touches about 11% of population of Western Europe. Tinnitus, as the complex symptom, is associated with other an-
noying ear disorders. While indication of its reason is very often impossible, the factors contributing to the development
of disorder were determined. Several theories explaining the mechanism of tinnitus have showed that extensive levels of
nervous system may be involved in its generation. Although no convincing treatment is available, some alleviating therapies
are recommended. They can be divided into two categories: relieving of its severity and reduction of its intensity.
Keywords: Tinnitus; Characteristics; Causes; Mechanisms; Therapy; Pharmacology.
*Corresponding Author:
Zoa A. Dziuganowska,
Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wybrzeże Wyspiańskiego 27, Wrocław, 50-370, Poland.
E-mail: zoa.a.dziuganowska@gmail.com
zoa.a.dziuganowska@pwr.edu.pl
Received: December 11, 2015
Accepted: January 29, 2016
Published: February 03, 2016
Citation: Zoa A. Dziuganowska (2016) Tinnitus - Characteristics and Therapy. Int J Bioorg Chem Mol Biol. 4(2), 17-23.
Copyright: Zoa A. Dziuganowska© 2016. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,
distribution and reproduction in any medium, provided the original author and source are credited.
Zoa A. Dziuganowska (2016) Tinnitus - Characteristics and Therapy. Int J Bioorg Chem Mol Biol. 4(2), 17-23.
18
OPEN ACCESS http://scidoc.org/IJBCMB.php
Such classication simplied diagnosis and allowed proposing
one denition of disorder as “the perception of sound that results
exclusively from activity within the nervous system without any corresponding
mechanical, vibratory activity within the cochlea, and not related to external
stimulation of any kind[5].
Sufferers describe the sound related to tinnitus as similar to cicadas,
crickets, winds, falling trap water, grinding steel, running engines,
escaping steam and etc. Most patients match their tinnitus to a
pitch above 3 kHz. However, tinnitus associated with Ménière’s
disease is usually low-frequency tone from 125 to 250 Hz [6].
Accompanying ailments
Tinnitus is often associated with other annoying symptoms
such as decreased sound tolerance, hyperacusis (an abnormally
strong reaction to sound occurring within the auditory pathways),
phonophobia (a fear of certain sounds) and misophonia (the
aversion to sounds). Moreover, it frequently coexists with hearing
loss or Ménière’s disease.
Tinnitus has also inuence on mental condition of sufferers as
it causes stress, annoyance, anxiety or even depression [7]. It also
increases difculties in concentration and decreases the quality of
sleep [8].
Epidemiology of tinnitus
The epidemiological studies of tinnitus are difcult because of
very broad denition of disorder. Furthermore, this subjective
perception differs from patient to patient what makes preparation
of questionnaire very complicated.
Tinnitus has become the public health problem. It touches about
10% of population in Great Britain, 14.2% in Sweden, 8.4% in
USA, 15.1% in Norway [9], 13% in Germany [10], 8% in France
[11] and 20.1% in Poland [12] (Figure 1).
The frequency of occurrence of tinnitus increases with age as
about 18% of population older than 70-years old suffer from
this ailment [13]. The disorder was also observed in children and
youngsters when the percentage of patients varied from 7% to
34% of population of this age group [14].
The causes of tinnitus
While indication of the reason of tinnitus is very often not
possible, the factors contributing to the development of disorder
were determined. The major causes are accumulated noise
exposure, acoustic trauma [15] and age-related changes [16]. The
other disorders which can provoke it are: occlusion of the ear
canal, external, middle ear and internal ear otitis, cholesteatoma,
otosclerosis, Ménière’s disease, alteration in blood ow,
barotrauma and head trauma [17]. Vestibular schwannoma [18],
microvascular compression of the vestibulocochlear nerve [19]
and cerebrovascular diseases [20] also can lead to tinnitus. The
other factors are jaw and neck disorders or temporomandibular
joint dysfunction [21].
Tinnitus can be also a side effect of taking some medicines,
for example analgesics like salicylates and non-steroidal anti-
inammatory agents. Moreover, the use of antibiotics such as
aminoglycosides (gentamycin, streptomycin and neomycin),
erythromycin, azithromycin, vancomycin, tetracycline and
chloramphenicol evokes tinnitus. It can be the side effect of
treatment with antineoplastic agents (bleomycin, cisplatinum,
methotrexate and vincristine), loop diuretics (bumetanide,
ethacrynic acid and furosemide), tricyclic antidepressants
(amitryptylline, doxepin and imipramine) and quinine or
chloroquine [22]. Finally, severe stress also causes tinnitus [6].
Pathophysiology of tinnitus
Tinnitus is the complex symptom, therefore, extensive levels of
nervous system can be involved in mechanism of its generation.
At the beginning, tinnitus was treated as spontaneous otoacoustic
emissions. They are small acoustic signals which appear in the
ear canal when tympanic membrane received vibrations from
cochlea [6]. However, since spontaneous acoustic emissions can
be measured by means of special equipment, thus, they cannot be
treated as tinnitus.
The discordant dysfunction/damage theory proposes the other
mechanism of generation of tinnitus [5]. The discordant damage
of sensory cells in the mammalian auditory epithelium (one
type of sensory cells – outer hair cells - is more dysfunctional
Figure 1. Epidemiology of tinnitus.
0
5
10
15
20
25
Great
Britain
Sweden USA Norway Germany France Poland
% population
Zoa A. Dziuganowska (2016) Tinnitus - Characteristics and Therapy. Int J Bioorg Chem Mol Biol. 4(2), 17-23.
19
OPEN ACCESS http://scidoc.org/IJBCMB.php
than the other type of sensory hair cells-inner hair cells) leads
to deregulation of sound transduction. This results in abnormal
activity within the auditory pathways that can cause tinnitus.
Generation of the symptom can be also the result of hyperactivity
of dorsal cochlear nucleus [23]. Interestingly, neuroimaging
techniques showed that reorganization of the auditory cortex,
caused by head or cochlea injuries, relates to tinnitus [24, 25].
Cross-talk theory postulates that disease can be the effect of
spontaneous activity of auditory neurons connected by articial
synapses (called “crosstalk”) that could be formed after damage
of auditory nerve bers [6].
The alternative mechanism concerns alterations of intracellular
Ca2+ concentration. Cytosolic concentration of Ca2+ affects
electromotility, therefore sensitivity of outer hair cells. Thus, any
abnormality in Ca2+ concentration may cause deregulation of
proper functioning of outer hair cells (the cochlear amplier) that
may evoke tinnitus of cochlear origin [26].
Tinnitus may be also caused by anomalies in neurotransmission
in inner hair cells [27]. Glutamate and aspartate (Figure 2) imitate
the effect of acoustic stimulation by increasing the spontaneous
activity of neurons of auditory nerve. Two classes of glutamate
receptors ionotropic (ligand gated ion channels) and metabotropic
(G-protein coupled) ones are related to this mechanism.
The expression of AMPA (α-amino-3-hydroxy-5-methyl-4-
isoxazolepropionate) (subunits: GluA2-4) and kainate (subunits:
GluK1-3, previous nomenclature GluK5-7) receptors in
auditory nerve cells is well acknowledged [28] (Figure 2). AMPA
receptors are responsible for high AMPA, kainate and glutamate
excitotoxicity. AMPA and kainate cause acute destruction of
dendrites of neurons of the auditory nerve. The other group of
ionotropic glutamate receptors, NMDA (N-methyl-D-aspartate)
(Figure 2) receptor (subunits: GluN1, GluN2B, GluN2C,
GluN2D), is also expressed in auditory nerve [29]. Behavioral
tests on animals, later conrmed by electrophysiological studies,
showed that while salicylate, which induces tinnitus, increases the
activity of NMDA receptors, NMDA antagonist blocks this effect
[30].
Metabotropic glutamate receptors are also expressed in the
cochlea. Although their role still remains unknown [27], they have
inuence on activity of neurons and they are related to the sound-
evoked suppression of neuronal ring in the auditory system [31].
The mechanism of generation of tinnitus is also connected with
the activity of GABA (γ-aminobutyric acid) (Figure 2) receptor
[32]. Behavioral tests showed that GABA agonist attenuates
chronic noise-induced tinnitus. Other studies on animals with
induced tinnitus indicated modications in the activity of choline
acetyltransferase and cholinergic receptors in the cochlear nucleus
[33].
The mechanism of manifestation of tinnitus can be also related
to dysfunction of serotonin (5-HT) (Figure 2) at one or more
levels in the central nervous system [34]. Tinnitus activates the
same cerebral structures as dopaminergic pathways, therefore
substances active towards dopamine receptors may also effect on
its severity [35].
The neurophysiological model of tinnitus, although it does not
explain the mechanism of its generation, postulates that apart
from the auditory system, the number of other systems in brain
are involved in its manifestation [5]. Moreover, it emphasizes
interactions between the auditory system and emotional (limbic)
and autonomic nervous system.
Treatment of Tinnitus
The methods of treatment of tinnitus can be divided into two
categories: relieving of its severity and reduction of its intensity.
Cognitive behavioral therapy, sound therapies, Tinnitus Retraining
Therapy, hearing aids, massage and stretching belong to the rst
group while electrical or magnetic stimulation and surgeries to the
second one. Pharmacotherapy can be included in both categories.
Pharmacotherapy
Pharmacotherapy of tinnitus differs depending on its type.
Despite various approaches to the treatment of the symptom,
FDA (Food and Drug Administration) or EMA (European
Medicine Agency) [36, 37] have not yet approved any drug.
One of effective substances is lidocaine (Figure 3), a local
Figure 2. Neurotransmitters and substances related to manifestation of tinnitus.
HO OH
NH2NH2
O O
OH
HO O
O
N
HO
OHN
OH
OH
HO
O
O
H2NO
O
N
NH2
N
H
HO
HO
NH2
O
OH
OH
dopamine salicylic acid
GABA acetylocholine serotonin
glutamic acid AMPA NMDA
Zoa A. Dziuganowska (2016) Tinnitus - Characteristics and Therapy. Int J Bioorg Chem Mol Biol. 4(2), 17-23.
20
OPEN ACCESS http://scidoc.org/IJBCMB.php
anaesthetic and anti-arrhythmic agent [38]. Given intravenously
or by intratympanic administration, lidocaine results in the
temporary disappearance of tinnitus or major change in its
severity in 70% of patients. However, because of its signicant
side effects, lidocaine is no longer used.
Although some antidepressants provoke tinnitus, the other
ones are commonly prescribed for its treatment [39]. Among
tricyclic antidepressants (Figure 3) - amitriptyline, trimipramine
and nortriptyline – only nortriptyline decreases both tinnitus and
depression. However, it is less effective in case of non-depressive
patients.
The activity of selective serotonin reuptake inhibitors – paroxetine
and sertraline was also investigated towards tinnitus (Figure 4).
While sertraline reduces its loudness and severity, the combination
of paroxetine with vestipitant (neurokinin-1 receptor P substance
antagonist) or vestipitant alone are even more effective and thus
they undergo clinical trials [40].
Benzodiazepines, allosteric modulators of the GABAA receptor,
were also considered as the treatment for tinnitus [41]. Clonazepam
(Figure 4) signicantly decreases tinnitus symptoms in 32% of
patients. However, treatment with benzodiazepines is restricted
because of high risk of drug addiction.
As it was mentioned, tinnitus may be caused by overstimulation of
glutamate receptors, exactly NMDA receptors. Behavioral studies
showed that NMDA receptor antagonists such as ifenprodil
[42], MK-801 (dizocilpine), 7-chlorokynurenate and gacyclidine
(Figure 5) [30] reduce its occurrence.
Therefore, the activity of many NMDA antagonists has been
also investigated. Among them, acamprosate, which acts both on
NMDA (as antagonist) and GABA receptors (as agonist), decreases
the severity of the symptom in more than 80% of patients [43].
The other NMDA and nicotinic acetylcholine receptor antagonist,
neramexane, is effective and undergoes III phase of clinical trials
[44] (Figure 5). Gacyclidine, earlier mentioned compound, is also
regarded as potential drug against tinnitus [45, 46].
Compounds active towards dopamine receptors (Figure 6) were
also proposed for the treatment of tinnitus [41]. A double-blind
placebo-controlled study indicated that sulpiride signicantly
decreases its severity. Moreover, combination of sulpiride with
hydroxyzine or melatonin intensies the effectiveness of the
treatment. The combination of the other compounds from this
category, upenthixol with clonazepam, is as active as clonazepam
alone and is already during clinical trials.
Studies on anticonvulsants [47] (Figure 7) showed that
carbamazepine is effective only if tinnitus derives from
neurovascular conict while the other compound, gabapentin,
only when the disorder origins from acoustic trauma [48].
The loop inhibiting diuretic, furosemide (Figure 7), given
intravenously, reduces the severity of this symptom in 50%
of patients. Moreover, studies indicated that it affects tinnitus
connected with Ménière’s disease. However, high doses of
compound may induce temporary hearing loss and recovery of
tinnitus [41].
The activity of other substances towards tinnitus was also studied.
For example, misoprostol (Figure 8), a synthetic prostaglandin
E1 analogue, is effective and safe medicine in therapy of this
symptom in hypertensive and/or diabetic patients [49]. Although
the rst clinical trials of nimodipine (Figure 8), calcium channel
blocker, suggested its positive effect on tinnitus patients, the
second trials did not conrmed this result [40]. Melatonin (Figure
8), a neurohormone that inuences sleep cycle and circadian
Figure 3. The structure of lidocaine and tricyclic antidepressants.
N
H
N
O
N N
N
NH
lidocaine amitriptyline trimipramine nortryptyline
Figure 4. Selective serotonin reuptake inhibitors, vestipitant and benzodiazepine.
N
H
Cl
Cl
O
O
OH
H
N
H
F
F
F
F
HN
N N
O
F
FF
F
F
F
F
O2N
N
H
N
O
Cl
sertraline paroxetine
vestipitant clonazepam
Zoa A. Dziuganowska (2016) Tinnitus - Characteristics and Therapy. Int J Bioorg Chem Mol Biol. 4(2), 17-23.
21
OPEN ACCESS http://scidoc.org/IJBCMB.php
Figure 5. NMDA antagonists for treatment of tinnitus.
N
HO
OH
HN
OH
Cl N
MK-801
(dizocilpine) 7-chlorokynurenate
CO2H
N
S
gacyclidine acamprosate neramexane
N
H
O
O
O
S
HO
NH2
ifenprodil
sulpiride hydroxyzine
upenthixol
S
OO
H2N
O
O
N
H
HNN
N
H
OOH
Cl
N
NOH
CF3
S
Figure 6. Compounds active on dopamine receptors.
Figure 7. Anticonvulsants and loop inhibiting diuretic – furosemide.
carbamazepine gabapentin furosemide
NH2
N
ONH2
OH
O
O
HN
Cl
OO
NH2
S
OH
O
Figure 8. Other compounds used to treat tinnitus.
misoprostol nimodipine
melatonin
O
OH
O
O
HO
O
O
N
H
OO
O
NO2
N
N
H
H
O
O
Zoa A. Dziuganowska (2016) Tinnitus - Characteristics and Therapy. Int J Bioorg Chem Mol Biol. 4(2), 17-23.
22
OPEN ACCESS http://scidoc.org/IJBCMB.php
rhythm, has also a positive effect on the disorder. Although it
does not reduce the loudness and frequency of the symptom, it
improves the quality of sleep in tinnitus patients [50]. However, it
is effective only in combination with sulpiride [40].
The other substances, mostly natural ones, were also studied for
the treatment for tinnitus. Zinc, for example, has relieving effect
but only on patients with hypozincemia [51]. Gingko biloba
extract is frequently prescribed for tinnitus patients [52] and
the standardized EGb 761® extract is under clinical trials. Some
other herbs such as Cimicifuga racemosa, Cornus ofcinalis, Verbascum
densiorum and herbal mixture called Yoku-kan-san have similar
effect to Gingko biloba [53]. Even botulinum toxin type A decreases
the severity of tinnitus [54] as it reduces inputs from cervical,
frontal, temporal and periauricular muscles.
Non-pharmacological therapies
There are also non-pharmacological treatments available:
cognitive behavioral therapy, sound therapy, Tinnitus Retraining
Therapy, hearing aids, the massage and stretching, and other,
more invasive techniques.
Cognitive behavioral therapy consists of two components: the
cognitive restructuring, based on identifying and modifying
negative thoughts concerning tinnitus, and the behavioral
modication promoting habituation to tinnitus by positive
imagery, attention control and relaxation [55]. The method is
efcient especially in cases when tinnitus leads to severe stress,
anxiety or depression [56].
The sound therapy is based on using normal natural sounds
from the environment such as streams, rain wind or etc. Such
treatment decreases the strength of tinnitus-related activity within
the auditory system [57]. Tinnitus Retraining Therapy relies on
the neurophysiological model of tinnitus. The rst step, retraining
teaching/counseling, aims at reclassication of tinnitus sound to
the neutral sound (not provoking negative emotions). The second
step is the sound therapy [58].
The use of hearing aids is effective only if tinnitus is accompanied
by hearing loss [59]. As tinnitus sometimes derives from jaw and
neck disorders or temporomandibular joint dysfunction, the
massage and stretching of these parts of the body can bring relief
[21].
The efcacy of other techniques such as repetitive transcranial
magnetic stimulation [60] and electrical stimulation [61] of auditory
cortex still requires further investigation. Surgical techniques,
still controversial, such as microvascular decompression of
cochleovestibular nerve are rarely performed [62].
Conclusion
Tinnitus is the complex disorder and although all pathophysiological
mechanisms of its generation are related to dysfunction of
auditory nerve and/or dysfunction in transmission of acoustic
signal, it is hard to determine which of them may be the most
plausible. It might be also possible that all of them are connected
with each other or one might trigger the another. Therefore,
proposing therapy should be based on detailed examination and
individual approach. It seems that combining pharmacological
treatment with non-pharmacological one may be the most
successful. However, as the mechanism of tinnitus is still not fully
understood, more investigation should be performed to explain it.
References
[1]. Dietrich S (2004) Earliest historic reference of 'tinnitus' is controversial. J
Laryngol Otol 118(7): 487-488.
[2]. Dan B (2005) Titus's tinnitus. J Hist Neurosci 14(3): 210-213.
[3]. Stephens SD (1984) e treatment of tinnitus-a historical perspective. J Lar-
yngol Otol 98(10): 963-972.
[4]. Jastrebo PJ (1990) Phantom auditory perception (tinnitus): mechanisms of
generation and perception. Neurosci Res 8(4): 221-254.
[5]. Jastrebo PJ, Hazell JW (2004) Tinnitus Retraining erapy, Implementing
the Neurophysiological Model. Cambridge University Press.
[6]. Han BI, Lee HW, Kim TY, Lim JS, Shin KS (2009) Tinnitus: characteristics,
causes, mechanisms, and treatments. J Clin Neurol 5(1): 11-19.
[7]. Langguth B, Kleinjung T, Fischer B, Hajak G, Eichhammer P, et al. (2007)
Tinnitus severity, depression, and the big ve personality traits. Prog Brain
Res 166: 221-225.
[8]. Hébert S, Fullum S, Carrier J (2011) Polysomnographic and quantitative
electroencephalographic correlates of subjective sleep complaints in chronic
tinnitus. J Sleep Res 20(1 Pt 1): 38-44.
[9]. Møller AR (2011) Texbook of Tinnitus. Epidemiology of Tinnitus in Adults.
Springer-Verlag, New York. 29-37.
[10]. Pilgramm M, Rychlick R, Lebisch H, Siedentop H, Goebel G, Kirchho D
(1999) Tinnitus in the Federal Republic of Germany: a representative epi-
demiological study. Proceedings of the Sixth International Tinnitus Seminar,
London. 64-72.
[11]. Bouccara D (2007) d’ENT World 4: 15.
[12]. Fabijańska A, Rogowski M, Bartnik G, Skarżyński H (1999) Epidemiology
of tinnitus and hyperacusis in Poland. Proceedings of the Sixth International
Tinnitus Seminar, e Tinnitus and Hyperacusis Centre: London. 569-571.
[13]. Sanchez L, Boyd C, Davis A (1999) Proceedings of the Sixth International
Tinnitus Seminar. ed. Hazell J 58–63, e Tinnitus and Hyperacusis Centre:
London.
[14]. Coelho CB (2011) Texbook of Tinnitus. Epidemiology of Tinnitus in Chil-
dren. Springer-Verlag, New York. 39-45.
[15]. Syka J (2002) Plastic Changes in the Central Auditory System After Hear-
ing Loss, Restoration of Function, and During Learning. Physiol Rev 82(3):
601-636.
[16]. Møller AR (2011) Texbook of Tinnitus. Cochlear and Non-cochlear Age-
Related Hearing Loss and Tinnitus. Springer, New York. 293-300.
[17]. Baracca G, Del Bo L, Ambrosetti U (2011) Texbook of Tinnitus. Tinnitus
and Hearing Loss. Springer, New York. 285-291.
[18]. Gimsing S (2010) Vestibular schwannoma: when to look for it? J Laryngol
Otol 124(3): 258-264.
[19]. De Ridder D, Møller AR (2011) Texbook of Tinnitus ed. Møller AR, Lang-
guth B, De Ridder D, Kleinjung T, Microvascular Compression of the Vesti-
bulocochlear Nerve. Springer, New York. 327-335.
[20]. Láinez MJA, Ponz A, Piera A (2011) Texbook of Tinnitus ed. Møller AR,
Langguth B, De Ridder D, Kleinjung T, Causes of Tinnitus: Cerebrovascular
Diseases. Springer, New York. 337-342.
[21]. Bjorne A (2007) Assessment of temporomandibular and cervical spine disor-
ders in tinnitus patients. Prog Brain Res 166: 215-219.
[22]. Holmes S, Padgham ND (2011) ''Ringing in the ears'': narrative review of
tinnitus and its impact. Biol Res Nurs 13(1): 97-108.
[23]. Kaltenbach JA, Godfrey DA (2008) Dorsal cochlear nucleus hyperactivity
and tinnitus: are they related? Am J Audiol 17(2): S148-161.
[24]. Mühlnickel W, Elbert T, Taub E, Flor H (1998) Reorganization of auditory
cortex in tinnitus. Proc Nat Acad Sci USA 95(17): 10340-10343.
[25]. Eggermont JJ, Roberts LE (2004) e neuroscience of tinnitus. Trends Neu-
rosci 27(11): 676-682.
[26]. Sziklai I (2004) e signicance of the calcium signal in the outer hair cells
and its possible role in tinnitus of cochlear origin. Eur Arch Otorhinolaryn-
gol 261(10): 517-525.
[27]. Puel JL (1995) Chemical synaptic transmission in the cochlea. Prog Neuro-
biol 47(6): 449-476.
[28]. Ruel J, Bobbin RP, Vidal D, Pujol R, Puel JL (2000) e selective AMPA
receptor antagonist GYKI 53784 blocks action potential generation and ex-
citotoxicity in the guinea pig cochlea. Neuropharmacology 39(11): 1959-
1973.
[29]. Ruel J, Chabbert C, Nouvian R, Bendris R, Eybalin M, et al. (2008) Salicy-
late enables cochlear arachidonic-acid-sensitive NMDA receptor responses. J
Zoa A. Dziuganowska (2016) Tinnitus - Characteristics and Therapy. Int J Bioorg Chem Mol Biol. 4(2), 17-23.
23
OPEN ACCESS http://scidoc.org/IJBCMB.php
Neurosci 28(29): 7313-7323.
[30]. Guitton MJ, Caston J, Ruel J, Johnson RM, Pujol R, et al. (2003) Salicylate
induces tinnitus through activation of cochlear NMDA receptors. J Neurosci
23(9): 3944-3952.
[31]. Voytenko SV, Galazyuk AV (2011) mGluRs modulate neuronal ring in the
auditory midbrain. Neurosci Lett 492(3): 145-149.
[32]. Brozoski TJ, Caspary DM, Bauer CA, Richardson BD (2010) e eect of
supplemental dietary taurine on tinnitus and auditory discrimination in an
animal model. Hear Res 270(1-2): 71-80.
[33]. Mellott JG, Motts SD, Schoeld BR (2011) Multiple origins of cholinergic
innervation of the cochlear nucleus. Neuroscience 180: 138-147.
[34]. Simpson JJ, Davies WE (2000) A review of evidence in support of a role for
5-HT in the perception of tinnitus. Hear Res 145(1-2): 1-7.
[35]. Fornaro M, Martino M (2010) Tinnitus psychopharmacology: A compre-
hensive review of its pathomechanisms and management. Neuropsychiatr
Dis Treat 6: 209-218.
[36]. Langguth B, Elgoyhen AB (2012) Current pharmacological treatments for
tinnitus. Expert Opin Pharmacother 13(17): 2495-2509.
[37]. http://www.ata.org/research-toward-cure
[38]. Trellakis S, Lautermann J, Lehnerdt G (2007) Lidocaine: neurobiological
targets and eects on the auditory system. Prog Brain Res 166: 303-322.
[39]. Robinson S (2007) Antidepressants for treatment of tinnitus. Prog Brain
Res 166: 263-271.
[40]. Elgoyhen AB, Langguth B (2011) Texbook of Tinnitus. Pharmacological
Approaches to Tinnitus Treatment. Springer, New York. 625-637.
[41]. Langguth B, Salvi R, Elgoyhen AB (2009) Emerging pharmacotherapy of
tinnitus. Expert Opin Emerg Drugs 14(4): 687-702.
[42]. Guitton MJ, Dudai Y (2007) Blockade of cochlear NMDA receptors pre-
vents long-term tinnitus during a brief consolidation window after acoustic
trauma. Neural Plast 2007: 1-11.
[43]. Sharma DK, Kaur S, Singh J, Kaur I (2012) Role of acamprosate in sensori-
neural tinnitus. Indian J Pharmacol 44(1): 93-96.
[44]. Suckfüll M, Althaus M, Ellers-Lenz B, Gebauer A, Görtelmeyer R, et al.
(2011) A randomized, double-blind, placebo-controlled clinical trial to
evaluate the ecacy and safety of neramexane in patients with moderate to
severe subjective tinnitus. BMC Ear Nose roat Disord 11: 1-10.
[45]. Wenzel GI, Warnecke A, Stöver T, Lenarz T (2010) Eects of extracochlear
gacyclidine perfusion on tinnitus in humans: a case series. Eur Arch Otorhi-
nolaryngol 267(5): 691-699.
[46]. Lobl JT, Schloss VJ (2009) Patent WO2009155421A1, published also as
EP2306839A4 or EP 2306839 A1, Neurosystec Corporation, Jun 18.
[47]. Levine RA (2006) Typewriter tinnitus: a carbamazepine-responsive syn-
drome related to auditory nerve vascular compression. ORL J Otorhi-
nolaryngol Relat Spec 68(1): 43-47.
[48]. Elgoyhen AB, Langguth B (2010) Pharmacological approaches to the treat-
ment of tinnitus. Drug Discov Today 15(7-8): 300-305.
[49]. Akkuzu B, Yilmaz I, Cakmak O, Ozluoglu LN (2004) Ecacy of misopros-
tol in the treatment of tinnitus in patients with diabetes and/or hyperten-
sion. Auris Nasus Larynx 31(3): 226-232.
[50]. PiccirilloJF (2007) Melatonin. Prog Brain Res 166: 331-333.
[51]. Coelho CB, Tyler R, Hansen M (2007) Zinc as a possible treatment for tin-
nitus. Prog Brain Res 166: 279-285.
[52]. von Boetticher A (2011) Ginkgo biloba extract in the treatment of tinnitus:
a systematic review. Neuropsychiatr Dis Treat 7: 441-447.
[53]. Enrico P, Sirca D, Mereu M (2007) Antioxidants, minerals, vitamins, and
herbal remedies in tinnitus therapy. Prog Brain Res 166: 323-330.
[54]. Lainez MJ, Piera A (2007) Botulinum toxin for the treatment of somatic
tinnitus. Prog Brain Res 166: 335-338.
[55]. Greimel KV, Kröner-Herwig B (2011) Texbook of Tinnitus. Cognitive Be-
havioral Treatment (CBT). Springer, New York. 557-561.
[56]. Hesser H, Weise C, Westin VZ, Andersson G (2011) A systematic review
and meta-analysis of randomized controlled trials of cognitive-behavioral
therapy for tinnitus distress. Clin Psychol Rev 31(4): 545-553.
[57]. Jastrebo MM (2007) Sound therapies for tinnitus management. Prog Brain
Res 166: 435-440.
[58]. Jastrebo PF, Jastrebo MM (2006) Tinnitus retraining therapy: a dierent
view on tinnitus. ORL J Otorhinolaryngol Relat Spec 68(1): 23-30.
[59]. Del Bo L, Ambrosetti U (2007) Hearing aids for the treatment of tinnitus.
Prog Brain Res 166: 341-345.
[60]. Langguth B, Kleinjung T, Landgrebe M, de Ridder D, Hajak G (2010)
rTMS for the treatment of tinnitus: the role of neuronavigation for coil po-
sitioning. Neurophysiol Clin 40(1): 45-58.
[61]. De Ridder D, De Mulder G, Menovsky T, Sunaert S, Kovacs S (2007) Elec-
trical stimulation of auditory and somatosensory cortices for treatment of
tinnitus and pain. Prog Brain Res 166: 377-388.
[62]. Yap L, Pothula VB, Lesser T (2008) Microvascular decompression of cochle-
ovestibular nerve. Eur Arch Otorhinolaryngol 265(8): 861-869.
ResearchGate has not been able to resolve any citations for this publication.
Article
Full-text available
1. Microvascular contacts or compressions of the vestibulocochlear nerve can result in tinnitus. 2. For nonpulsatile tinnitus, the contact is most often at the central nervous system segment. 3. For pulsatile tinnitus and typewriter tinnitus, the contact is at the peripheral nervous system segment. The tinnitus is unilateral and characterized by intermittent paroxysms of tinnitus. (a) A typical development consists of progressively more frequent bouts of tinnitus, which last longer and longer. (b) If bilateral vascular compressions exist, the tinnitus alternates between the left and right side, and does not occur on each side simultaneously. 4. Associated symptoms are correlated with related contacts/compressions of nearby nerves and include overt or cryptogenic hemifacial spasms, geniculate neuralgia, optokinetically induced short bouts of disabling positional vertigo, and tinnitus frequency-specific hearing loss. 5. Auditory brainstem responses (ABRs) correlate with disease progress and clinical symptoms and can be used diagnostically. (a) Tinnitus is causally related to a decrease in amplitude of peak II in the ipsilaterally elicited ABR. (b) Tinnitus frequency-specific hearing loss is causally related to prolongation of the ipsilateral interpeak latency (IPL) I–III. (c) Prolongation of contralateral IPL III–V occurs and is a sign of slowed signal transmission in the brainstem. 6. Magnetic resonance imaging sequences with constructive interference in steady state can visualize most vascular contacts/compressions of the auditory nerve. 7. Microvascular decompression should be performed before irreversible nerve damage is induced; clinically, the procedure should be performed before 4–5 years.
Chapter
Full-text available
1. Age-related changes are some of the most common causes of disorders of sensory systems. 2. The most common age-related change in hearing is elevation of the hearing threshold beginning at the highest audible frequencies, progressing toward lower frequencies while deepening. 3. Age-related changes in hearing are often, but not always, accompanied by tinnitus. 4. Age-related changes in hearing function may be caused by: (a) Degeneration of sensory receptor cells, in the cochlea (b) Change in the conduction velocity of sensory nerve fibers (c) Change in the access to neural transmitters, such as gamma amino butyric acid (GABA), and subsequent increases in GABA receptor sites 5. Change in processing of information may also occur, causing deterioration of speech comprehension. 6. Animal studies have shown that the progression of age-related changes in hearing might be affected (slowed down) by exposure to sound (“enhanced sound environment”) indicating expression of neural plasticity plays a role in some age-related changes of sensory functions. 7. The large individual variability in age-related changes in hearing has many causes, such as exposure to loud sounds, environmental factors, genetics, different expression of genes (epigenetics), and unknown factors.
Chapter
Full-text available
1. Many studies have addressed the prevalence of tinnitus, but the definition of tinnitus has varied. 2. Some studies have reported that as many as 80% of the adult population experience tinnitus at some point. 3. Six large population studies in different countries reported prevalence of prolonged tinnitus, varying between 4.4 and 15.1% for adults and between 7.6 and 20.1% for individuals below the age of 50 years. One of the studies reported that 2.4% of the population responded “yes” to the description of tinnitus as “tinnitus plagues me all day.” 4. A study in four cities in England found that tinnitus, on average, occurred in 17.5% of the participants in the age group of 40–60 years and 22.2% in participants above the age of 60 years. 5. Since tinnitus has many forms and its prevalence varies with age and, to some extent, gender, the prevalence of tinnitus cannot be described by a single number. 6. The prevalence of tinnitus increases monotonically up to the age of approximately 70 years, above which the prevalence either becomes constant or decreases slightly with age. 7. The prevalence of tinnitus is lower in women up to 75 years, above which the gender difference becomes small. 8. There is some evidence that noise exposure increases the risk of tinnitus. 9. The odds of having tinnitus increases with the degree of hearing loss when measured at 4 kHz. 10. While reported “trouble hearing” increases monotonically with age, “bothersome tinnitus” increases with age only up to the age group of 65–74, after which it becomes independent of age or decreases slightly with age.
Article
Full-text available
Acamprosate with dual mechanism of action as glutamate antagonist and GABA agonist can be a potential target to decrease the severity of sensorineural tinnitus. (1)To study the effectiveness of acamprosate in providing subjective relief and objective improvement in patients having tinnitus of sensorineural origin. (2) To evaluate the adverse events related to the use of acamprosate and also determine the change in quality of life (QOL) parameters. The study was randomized double-blind, placebo controlled, crossover. Forty adult subjects (>18 years of age), of either sex with tinnitus of sensorineural origin, were administered either acamprosate 333 mg TDS or matched placebo for a period of six weeks followed by a washout period of one week. Drug therapy was switched for another six weeks in consonance with the crossover design. The effect of acamprosate and placebo on subjective relief and objective improvement was evaluated by using modified tinnitus severity, QOL scores and audiometry with tinnitus matching in frequency and loudness. At the end of the study, the drug had shown a statistically significant improvement in reducing the tinnitus score in 92.5% of the patients and placebo with an improvement in 12.5% of the patients. The drug was well tolerated without any serious drug reactions. Acamprosate is an effective drug in treating the severity of sensorineural tinnitus without causing much of the side effects.
Article
Full-text available
Tinnitus is a symptom frequently encountered by ear, nose, and throat practitioners. A causal treatment is rarely possible, and drug and nondrug treatment options are limited. One of the frequently prescribed treatments is Ginkgo biloba extract. Therefore, randomized, placebo-controlled clinical trials of Ginkgo biloba extract preparations were searched for and reviewed systematically. There is evidence of efficacy for the standardized extract, EGb 761(®) (Dr Willmar Schwabe GmbH & Co KG Pharmaceuticals, Karlsruhe, Germany), in the treatment of tinnitus from three trials in patients in whom tinnitus was the primary complaint. Supportive evidence comes from a further five trials in patients with age-associated cognitive impairment or dementia in whom tinnitus was present as a concomitant symptom. As yet, the efficacy of other ginkgo preparations has not been proven, which does not necessarily indicate ineffectiveness, but may be due to flawed clinical trials. In conclusion, EGb 761(®), a standardized Ginkgo biloba extract, is an evidence-based treatment option in tinnitus.
Article
Introduction: Tinnitus, the phantom perception of sound, is a highly prevalent disorder and treatment is elusive. Areas covered: This review focuses on clinical research regarding pharmacological treatments for tinnitus. The authors searched PubMed databases for English language articles related to pharmacological treatment of tinnitus, published through August 2012. The keywords "tinnitus AND pharmacological treatment" and "tinnitus AND drugs" were used. The search focused on clinical trials, but was complemented by other articles and information from clinical trial registries. Expert opinion: Despite the significant unmet clinical need for a safe and effective drug for tinnitus relief, there is currently no EMA- or FDA-approved drug on the market. Even a drug that produces a small but significant effect would have a huge therapeutic impact. At present, evidence-based pharmacological approaches are limited to the treatment of comorbidities such as depression, anxiety, or insomnia. In the last few years there have been significant advances in the understanding of the pathophysiology of the different forms of tinnitus, the establishment of valid animal models, and the development of clinical trial methodology. A glimpse of hope is appearing in the horizon as an increasing number of pharmaceutical industries now have compounds targeting tinnitus in their pipeline.
Chapter
1. Children experience tinnitus and might present ­similar suffering as observed in adults but they rarely mention the symptom unless directly asked about it. 2. Difficulty on concentration, sleeping, hearing, leisure activities, sports practice, and hyperacusis are the most frequent complaints associated to tinnitus in children. 3. Only a few population studies have been performed and have disclosed prevalence rates from 6% to 59%. Many factors might be implicated in the large inter-study variability of tinnitus prevalence in children. 4. Age, gender, hearing loss, motion sickness, hyperacusis, and noise exposure have been suggested as risk factors to development of tinnitus in children. 5. A proper model to investigate children should be developed for the purpose of obtaining accurate information about the prevalence of tinnitus in children. 6. Preventive measures should aim at hearing education about the risk of hearing loss and tinnitus. Prevention of noise exposure should be promoted as early as possible.
Chapter
1. Damage in the external, middle, or internal ear can contribute to the emergence of tinnitus because of the hearing loss it causes.