Auditory Neural Plasticity in Tinnitus Mechanisms and Management

Abstract

Tinnitus, which is the perception of sound in the absence of a corresponding external acoustic stimulus, including change of hearing and neural plasticity, has become an increasingly important ailment affecting the daily life of a considerable proportion of the population and causing significant burdens for both the affected individuals and society as a whole. Here, we briefly review the epidemiology and classification of tinnitus, and the currently available treatments are discussed in terms of the available evidence for their mechanisms and efficacy. The conclusion drawn from the available evidence is that there is no specific medication for tinnitus treatment at present, and tinnitus management might provide better solutions. Therapeutic interventions for tinnitus should be based on a comprehensive understanding of the etiology and features of individual cases of tinnitus, and more high quality and large-scale research studies are urgently needed to develop more efficacious medications.

Figure 1

Possible therapeutic mechanism of TCAs on tinnitus. TCAs block the 5-HT_2A receptor, thus preventing 5-HT from binding to the 5-HT_2A receptor and activating the PLC-IP₃/DAG-PKC pathway and thus impairing downstream microtubule-dependent glycine receptor transport. This in turn acts as a barrier to glycine receptor binding on the surface of the cell membrane followed by a reduction of chloride influx and thus leading to a decrease in tonic current and an increase in intracellular potential and excitability. TCAs: tricyclic antidepressants; 5-HT_2AR:5-hydroxytryptamine receptor _2A receptor; PIP₂: phosphatidylinositol 4,5-bisphosphate; PLC: phospholipase C; DAG: diacylglycerol; PKC: protein kinase C; IP₃: inositol 1,4,5-trisphosphate.

Figure 2

Possible therapeutic mechanism of glutamate antagonists on salicylate-induced tinnitus. (a) Schematic diagram of the organ of Corti. (b) Salicylate can inhibit the electromotility of OHCs, which reduces the opening probability of MET channels, downregulates the influx of K⁺ through the MET channels, and increases the EP. The sets of three down and three up arrows represent the longitudinal extension of electromotility in OHCs. (c) The increased EP is followed by opening of the voltage-gated Ca²⁺ channels, fusion of the synaptic ribbon to the cytomembrane of the IHCs, and release of glutamate, and thus cochlear fibers depolarize abnormally and tinnitus occurs. Glutamate antagonists can inhibit the process by blocking AMPARs and NMDA receptors. IHC: inner hair cell; OHC: outer hair cell; EP: endocochlear potential; MET: mechanoelectrical transduction; NMDA receptor: N-methyl-D-aspartic acid receptor; AMPAR: α-amino-3-hydroxy-5-methyl-4-isoxazole-propionicacid receptor.