Can GABAkines quiet the noise? The GABAA receptor neurobiology and pharmacology of tinnitus

Witkin, Jeffrey M.; Lippa, Arnold S.; Smith, Jodi L.; Cook, James M.; Cerne, Rok

doi:10.1016/j.bcp.2022.115067

Cited by 4 publications

(2 citation statements)

References 168 publications

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“…Whatever the source, the Excess Central Gain model posits that disinhibition has the knock-on effect of increasing the synchrony and activity rate of local excitatory neurons in silence (the basis of the phantom sound) as well as disproportionately strong responses to moderately intense sound (the basis of loudness hypersensitivity) 25–29 . As expected, boosting levels of central inhibition through direct activation protocols in animals or GABA-acting drugs in humans can mitigate tinnitus symptoms 30,31 .…”

Section: Introductionsupporting

confidence: 63%

The human pupil and face encode sound affect and provide objective signatures of tinnitus and auditory hypersensitivity disorders

Smith,

Jahn,

Sugai

et al. 2023

Preprint

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SummaryCentral disinhibition works like an amplifier, boosting neural sensitivity to progressively weaker peripheral inputs arising from degenerating sensory organs. The Excess Central Gain model posits that central disinhibition also gives rise to cardinal features of sensory disorders including sensory overload and phantom percepts. Here, we tested predictions of this model with neural, autonomic, and behavioral approaches in participants with sound sensitivity and tinnitus (phantom ringing). We confirmed enhanced auditory neural gain but found no association with their sound aversion and anxiety. Instead, we hypothesized that symptom severity was linked to affective sound encoding. In neurotypical controls, emotionally evocative sounds elicited pupil dilations, electrodermal responses and facial reactions that scaled with valence. Participants with disordered hearing exhibited disrupted pupil and facial reactivity that accurately predicted their self-reported tinnitus and hyperacusis severity. These findings highlight auditory-limbic dysregulation in tinnitus and sound sensitivity disorders and introduce approaches for their objective measurement.

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Section: Introductionsupporting

confidence: 63%

The human pupil and face encode sound affect and provide objective signatures of tinnitus and auditory hypersensitivity disorders

Smith,

Jahn,

Sugai

et al. 2023

Preprint

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“…[5] [21,22] [ [23][24][25][26][27][28] surgical procedures, behavioral audio therapy, tinnitus masking devices, transcranial magnetic stimulation, and psychotherapy were also suggested. [1,3,16,19,29] The aim of this study is to investigate the use of clonazepam as an effective treatment for idiopathic tinnitus or to control the severity of its impact on patients' quality of life.…”

Section: Background and Objectivesmentioning

confidence: 99%

The Role of Clonazepam on the Control and Management of Tinnitus: A Cross-over randomized study.

Roumieh

Tarrab

Dandashli

et al. 2023

Preprint

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Background and objectives: Tinnitus is considered one of the most prevalent complaints among patients viewed at the E.N.T and neurological clinics. It’s defined as the perception of phantom sound, originated in the head. It’s estimated that 20% of population suffer tinnitus, 1% of which have severe symptoms affecting their quality of life, and may lead to suicide. In spite of that there is no “golden stander” test for tinnitus nor an agreed upon treatment or cure. Leaving practitioner trying with different protocols and medications for each patient. The paper search in the use of clonazepam as an effective treatment for tinnitus or at least as a tamer for the affects it has on patient’s quality of life. Methods: This is a cross-over study, conducted on 80 patients who completed the inclusion criterion and signed the informed consent paper. They were randomly divided into 2 groups. The 1st group had clonazepam for 1 month as the 1st stage then they were followed using the attached survey for 3 months, for the 2nd stage they had gingko biloba “herbal medication usually used on tinnitus cases” for 1 month then were followed for 2 weeks with the same survey. The 2nd group were reversed for the medications “ginkgo biloba for the 1st stage- clonazepam for the 2nd”. This study was designed for each patient to serve as their own case-control. Results: A significant improvement was found during the use of clonazepam “p value < 0.05” compared to their basic status on both scales THI+VAS. No improvement was seen during the use of gingko biloba. “p value >0.05” Conclusion: Clonazepam can be considered one of the effective medication for the treatment of subjective tinnitus, no matter how severe or chronic was it. It’s also advised to start to rely less on gingko biloba for the treatment of tinnitus.

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Stress‐Induced Tinnitus in a Rat Model: Transcriptomics of the Prefrontal Cortex and Hippocampus

Han,

Park,

Kim

et al. 2024

The Laryngoscope

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ObjectivesThe molecular mechanisms by which stress leads to the development of tinnitus are not yet well understood. This study aimed to identify brain changes in a stress‐induced tinnitus (ST) animal model through transcriptome analysis of the prefrontal lobe and hippocampus.MethodsTwenty Sprague–Dawley rats were subjected to restraint stress for 2 h. Following the gap prepulse inhibition of the acoustic startle (GPIAS) reflex test to assess tinnitus development, the prefrontal lobes and hippocampi of the brains were harvested from 15 rats: five with evident tinnitus (ST), five with noticeable non‐tinnitus (stress‐induced non‐tinnitus; SNT), and five without stress (control group). Comparative RNA‐seq analysis was conducted to examine gene expression profiles.ResultsIn comparison to the control group, the ST group exhibited 971 and 463 differentially expressed genes (DEGs) in the prefrontal lobe and hippocampus, respectively (FDR < 0.05). The SNT group showed a largely similar gene expression to the control group. Enrichment analysis of the prefrontal lobe revealed the downregulation of gene sets associated with neurotransmitter and synapse‐related functions and the upregulation of cell cycle‐related gene sets in the ST group. In the hippocampus, there were significantly downregulated gene sets associated with steroid production and upregulated gene sets related to the extracellular matrix in the ST group. Immune‐related gene sets were upregulated in both the prefrontal lobe and hippocampus.ConclusionOur research presents evidence that differences in genetic expression in the prefrontal lobe and hippocampus after exposure to stress play a significant role in the development of tinnitus.Level of EvidenceNA Laryngoscope, 2024

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Can GABAkines quiet the noise? The GABAA receptor neurobiology and pharmacology of tinnitus

Cited by 4 publications

References 168 publications

The human pupil and face encode sound affect and provide objective signatures of tinnitus and auditory hypersensitivity disorders

The human pupil and face encode sound affect and provide objective signatures of tinnitus and auditory hypersensitivity disorders

The Role of Clonazepam on the Control and Management of Tinnitus: A Cross-over randomized study.

Stress‐Induced Tinnitus in a Rat Model: Transcriptomics of the Prefrontal Cortex and Hippocampus

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