31+ Ways To Combat And Fix Tinnitus (With Mechanisms)

Tinnitus: The Phantom Perception 👻

 
tinnitus.jpg
 

In this post, we will discuss underlying mechanisms and pathologies of tinnitus, genetic predispositions, and effective ways to combat tinnitus.

Contents:

  1. Basics And Types Of Tinnitus
  2. My Experience With Tinnitus
  3. Common Pathologies
  4. Treatments For Tinnitus
  5. Mechanism Of Action
  6. Genetics

Basics And Types Of Tinnitus

Tinnitus is the perception of sound without external external sound present. R

Its prevalence is quite high, affecting up to 2% of the adult population (45 million American adults experience tinnitus and 15 million report frequent symptoms). R R

Tinnitus results usually from a disorder of the auditory system (usually peripheral, rarely central), the somatosensory system (head and neck), or a combination of the two. R

The type of sound occuring during tinnitus may vary: R

  • Location
  • Perception
  • Pitch
  • Pulsatile/clicking
  • Variability

Downsides Of Tinnitus

 
 https://www.ncbi.nlm.nih.gov/pubmed/26342399

https://www.ncbi.nlm.nih.gov/pubmed/26342399

 

Tinnitus can induce cognitive impairment, such as reduced working memory and attention. R R

For example, speech comprehension is impaired in patients with tinnitus, especially in the presence of competing noise. R

My Experience With Tinnitus

My hearing has always been spotty, due to lack of prefrontal cortex connections to interpret language.

Anyway, back in college, I attended a Bloody Beetroots concert at concert hall and stood next to a large speaker for most of the show.

The week after that concert, I could not hear out of my right ear and following that I had hollowness and tinnitus.

The tinnitus lasted for years after, but over the years my tinnitus has become much better, to the point that I only get ringing or phantom sounds a few times a year.

From this experience, I made it a standard for myself to always bring ear plugs when going to loud social events.

Common Pathologies

1. Acetylcholine/Choline

Impaired cholinergic functioning may contribute to tinnitus and activation of muscarinic (M1) acetylcholine (ACh) may provide some benefit for chronic tinnitus. R R

Technical:

  • Activation of M1 ACh induces neuroplaticity via BDNF and NGF, thus helping retrain nerves in the AC. R

2. Autoimmunity

Higher levels of autoimmune markers (via IL-1b) has been linked to some forms of tinnitus (such as Meniere's Disease). R R R R

3. Facial Nerve Compression

Compression of nearby cranial nerves (vascular contact/compression of the vestibulocochlear nerve) may induce tinnitus or similar symptoms and treatment for this is very amenable. R R

4. Hyperexictability, Glutamate And GABA

Usually in tinnitus, there is increased neuronal excitability and decreased inhibitory transmission in neurons. R

For example, glutamate (an excitatory neurotransmitter) may be overactive with little action of GABA (an inhibitory neurotransmitter) in the dorsal cochlear nucleus (DCN, a region of the brain interprets auditory signals). R

Technical:

  • A great example is after acoustic trauma, there can be a reduction in glutamic acid decarboxylase 65 (GAD65), an enzyme that helps produce gamma-aminobutyric acid (GABA), thus causing enhanced neuronal excitability in the DCN. R
  • GABA enhances tonic inhibition through high-affinity, non-inactivating extrasynaptic GABA receptors...most drugs that help tinnitus in animal models are active via tonic inhibition. R
  • The dysregulated amount of excitotoxic glutaminergic, glycinergic, and GABAergic actions may cause synaptic plasticity via AMPA and NMDA. R

5. Metabolic Diseases

There is a higher rate of developing tinnitus if suffering from metabolic diseases such as Chronic Kidney Disease (CKD), Diabetes, or Heart Failure. R

    6. Noise Exposure And Hyperacusis

     
    tinnitus noise.jpg
     

    High levels of noise exposure is ototoxic (toxic to the ear) and can damage nerves, thus leaving the tolerance for tinnitus onset a lot lower. R

    This form is the most common pathology of tinnitus. R

    Technical:

    • Individuals exposed briefly to loud noise, tinnitus onset is reported to occur immediately following the exposure...5 min equates to last around for nearly 15 min of tinnitus following the exposure. R

    7. Ototoxic Drugs

    Including salicylate-based drugs and memantine (more in below section) there are ototoxic drugs that can induce tinnitus: R

    • Acetazolamide
    • Adenosine
    • Almotriptan
    • Amikacin
    • Amiloride
    • Amitriptyline
    • Amphotericin
    • Aspirin
    • Azithromycin
    • Benzodiazapine withdrawals
    • Bexarotene
    • Capreomycin
    • Carbamazepine
    • Carboplatin
    • Cefpodoxime
    • Celecoxib
    • Chlorpheniramine
    • Ciprofloxacin
    • Cisplatin
    • Citalopram
    • Clarithromycin
    • Cotrimoxazole
    • Diclofenac
    • Diltiazem
    • Enalapril
    • Flecainide
    • Fosphenytoin
    • Frusemide
    • Ganciclovir
    • Hydroxychloroquine
    • Ibuprofen
    • Imipramine
    • Indomethacin
    • Irbesartan
    • Ketorolac
    • Lignocaine
    • Linezolid
    • Mefloquine
    • Metoprolol
    • Naproxen
    • Netilmicin
    • Nicardepine
    • Norfloxacin
    • Ofloxacin
    • Paclitaxel
    • Prazocin
    • Quinidine
    • Quinine
    • Ramipril
    • Sulindac
    • Tacrolimus
    • Teicioplanin
    • Tetracyclines
    • Timolol
    • Tobramycin
    • Tolbutamide
    • Torasemide
    • Trandolapril
    • Vancomycin
    • Vindesine
    • Zalcitabine

    8. Salicylates

    Salicylates are commonly used in models to induce tinnitus. R R R

    Eating a high intake of salicylates in diet or taking drugs like aspirin may contribute to the onset of tinnitus, hearing loss, and neurotoxicity. R R R

    Technical:

    • Following exposure to a high dose of sodium salicylate, tinnitus onset occurs between 1 and 3 h post exposure and typically dissipates within 1–2 days following the exposure. R
    • One reason for this is that salicylates potentiate NMDA receptors response, so taking drugs like memantine may have a similar response in auditory cortex (AC). R
    • Another reason for this is that salicylates decrease GAD, resulting in less GABA in auditory nerve transmission inhibition. R
    • Salicylates also cause an increase in corticosterone, which interacts with stress making tinnitus and hyperacusis worse. R
    • Salicylates (over the long term) cause ↑BDNF/CREB, upregulated synaptic efficacy, and changed synaptic ultrastructure in the AC.  R

    9. Serotonin

    Excess serotonin (5HT) can contribute to tinnitus.

    For example, selective serotonin reuptake inhibitors (SSRI), have shown to cause tinnitus as a byproduct of higher levels of serotonin in the brain. R

    Technical:

    • 5HT acts on the dorsal cochlear nucleus (DCN) and enhances excitability of the nerves and lowers their sensory threshold. R

    10. Smoking

    In multiple studies have concluded a strong significance between smoking (current, former, and ever) and tinnitus. R

    11. Stress

     
     https://link.springer.com/article/10.1007%2Fs00106-014-2973-7

    https://link.springer.com/article/10.1007%2Fs00106-014-2973-7

     

    All forms of stress (psychological, mental, physical, cellular) can contribute to tinnitus if it reaches the focal areas in the brain and/or auditory nerve. R

    For example, lack of sleep can be a stressor to induce tinnitus symptoms. R 

    Altering the hypothalamic-pituitary-adrenal (HPA) axis (via stress) increases prevalence of tinnitus and anxiety. R

    For example, in veterans with Post Traumatic Stress Disorder (PTSD), there are changes in histone acetylation and DNA methylation (hypomethylation), esp concerning glucocorticoid receptor gne (NR3C1). R

    Stress during pregnancy may also result in tinnitus for the offspring (via lower BDNF). R

    Technical:

    • The amygdala sends glutamatergic inputs to the NAc that serve as an arousal pathway, and the brainstem raphe nucleus sends serotonergic inputs to the NAc serving as a sleep-cycle pathway thus, generalized subcallosal atrophy could derive from emotional, sleep, arousal, habituation, and gating disorders. R
    • Stress activates HPA axis to release cortisol and adrenaline (epinephrine): adrenaline stimulates the sympathetic nervous system and reduces the activity of the parasympathetic nervous system, whereas cortisol induces gluconeogenesis as well as lipolysis and proteolysis... epigenetic changes in 5HT (SLC6A4), Glucoroticoid receptors (GR (NR3C1)), and GABA can increase the prevalence of tinnitus. R
    • 5H1AA and Norepinephrine (NE) are a lot higher in tinnitus patients. R

    12. Other Possible Pathologies

    Treatments For Tinnitus

    Essentially two major approaches can be taken: rehabilitating the sensory organ and reversing the central mechanisms of tinnitus. R

    Thus treatment for tinnitus depends on the type of pathology (above) as structural changes may have occurred (ie acoustic trauma leading to damage to hair cells). R

    Therapies

    Lifestyle:

    • Acupuncture at cervical Jiaji (EX-B 2) - helps with nervous tinnitus R
    • Cognitive Behavioral Therapy R
    • Hypnosis - needs more research R
    • Reduces salicylate intake R
    • Sound Therapy (such as phase cancellation or noise generators) R
    • Stress reduction techniques - increase BDNF/NGF, follow circadian rhythm, reduce stress metabolites (ACTH, cortisol, NE, 5-H1AA), activated NRF2 for oxidative stress (needs more research) R R
    • Tinnitus Retraining Therapy R R

    Supplements:

    • Chai-Hu-Jia-Long-Gu-Mu-Li-Tang (Radix Bupleuri, Fossilia Ossis Mastodi, Rhizoma Zingiberisrecens, Radix Ginseng, Poria, Radix Scutellariae, Concha Ostreae, Ramulus Cinnamomi, Rhizoma Pinelliae, Fructus Jujubae, Rhizoma Rhei) R
    • CoQ10 R
    • Er Ming Fang (Rehmannia glutinosa, Cornus officinalis, Salvia mittiorrhiza, Pueraria, Schisandra chinensis, Poria cocos and Platycodon grandiflorum) - may alleviate tinnitus associated with acoustic trauma R
    • N-acetyl homotaurine - helps with stress induced tinnitus R
    • Spirulina - helps with salicylate induced tinnitus R
    • Taurine - attenuates tinnitus and improves auditory discrimination by increasing inhibitory tone and decreasing noise in the auditory pathway R
    • Tian Ma/Gastrodin R R

    Hormones:

    Drugs:

    • AM-10 (NMDAR antagonist) R
    • Benzodiazepines R
    • Bromazepam R 
    • D(-)-2-amino-5-phosphonopentanoate (NMDAR antagonist) R
    • Estazolam R
    • Flumazenil R 
    • Gabapentin R
    • HDAC inhibition - geared towards stress-related tinnitus R
    • SSRIs (variable results esp when addressing stress) R
    • Vigabatrin (GABA agonist) R

    Devices/Surgical Options:

    • Cochlear implants R
    • Deep brain stimulation (caudate nucleus or NAC) R R
    • Hearing Aids R
    • Low Level Laser Therapy (LLLT) - effective in alleviating tinnitus in patients with noise-induced hearing loss, although this effect has faded after 3 months of follow-up R
    • TCMS (Noninvasive extracranial magnetic or electrical fields) R
    • TDCS R
    • Transcutaneous electrical stimulation of the head and neck (50% improvement in patients with somatic tinnitus) R
    • Vagus Nerve Stimulation + Auditory Stimulation - very effective (via M1ACh) R R

    Little or no effect:

    Mechanism Of Action

    The auditory system is divided grossly into central (upper) and peripheral (lower) divisions... The upper auditory pathway contains the primary auditory cortex (A1), medial geniculate bodies (MGBs), inferior colliculus (IC), superior olivary complex (SOC), and the cochlear nucleus complex (CN)...mechanical energy and motion is translated to release neurotransmitter (glutamic acid [Glu]) onto the dendrites of first-order afferent neurons, which then enter the brain via brainstem. R

    Most auditory nerve fibers synapse within the ipsilateral cochlear nuclei, which are tonotopically organized into anterior ventral cochlear nuclei (AVCN), dorsal cochlear nuclei (DCN), and posterior ventral cochlear nuclei (PVCN) divisions...The AVCN and PVCN process the temporal features of the transmitted signal using membrane capacitance, dendritic filtering, and spatial organization, whereas fusiform cells of the DCN contribute to decoding sound level and directional information. R

    Tinnitus normally resides from problems in the DCN, but this pathology can shift (adapt) to other brain regions, such as the IC and auditory thalamo-cortical system. R

    In chronic tinnitus after functional damage of the cochlea (i.e., noise or hearing loss) and consequent abnormal input to the higher level neural structures of the auditory pathway, there is stabilization of hyperpolarization of thalamic relay cells via a new neuroplasticity (possibly AMPA/NMDA) although acetylcholine muscarinic receptor type 1 (M1) regulating the expression of different neurotrophins (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) may play a role in stabilizing/reversal. R

    Sound-induced deflection of hair cell stereocilia affects mechanosensitive transducer channels at the apex of each hair cell...Deflection of stereocilia results in the release of Glu-containing vesicles at the hair base, and depolarization of primary afferent nerves – Glu serves as the primary excitatory neurotransmitter throughout ascending levels of the auditory system. R

    Genetics

    ADD1

    102680 (MIM)

    • The p.G460W heterozygous genotype (p = 0.009) and W allele (p = 0.021) are statistically significantly higher in patients than controls R

    KCNE1

    rs915539

    • Significance was detected in rs915539 (p = 0.005) in noise-resistant subjects and when comparing tinnitus patients vs. controls in noise-resistant and susceptible groups (p = 0.018) R

    KCTD12

    rs34544607 

    • rs34544607 was associated with tinnitus (p= 0.04) but weakened after screening 50 additional cases (p = 0.07) R 

    SLC12A2

    rs10089

    • Significance was detected in rs10089 (p = 0.016) in noise susceptible subjects and when comparing tinnitus patients vs. controls in noise-resistant and susceptible groups (p = 0.026) R

    SLC6A4 (5-HTTLPR)

    Unknown SNP

    • tinnitus patients with the (LL) variant of 5-HTTLPR assessed their insomnia, difficulties with concentration, and the severity of tinnitus as more disturbing than the patients with (LS) or (SS) allele did. R

    Other genetics:

    No associations found in ACE, BDNF, GDNF, KCNE3, and HTR1A. R R R