Salicylate-Induced Changes in Hearing Thresholds in Mongolian Gerbils Are Correlated With Tinnitus Frequency but Not With Tinnitus Strength

Abstract

Tinnitus is an auditory phantom percept without external sound sources. Despite the high prevalence and tinnitus-associated distress of affected patients, the pathophysiology of tinnitus remains largely unknown, making prevention and treatments difficult to develop. In order to elucidate the pathophysiology of tinnitus, animal models are used where tinnitus is induced either permanently by noise trauma or transiently by the application of salicylate. In a model of trauma-induced tinnitus, we have suggested a central origin of tinnitus-related development of neuronal hyperactivity based on stochastic resonance (SR). SR refers to the physiological phenomenon that weak subthreshold signals for given sensors (or synapses) can still be detected and transmitted if appropriate noise is added to the input of the sensor. The main objective of this study was to characterize the neurophysiological and behavioral effects during salicylate-induced tinnitus and compare these to the conditions within the trauma model. Our data show, in line with the pharmacokinetics, that hearing thresholds generally increase 2 h after salicylate injections. This increase was significantly stronger within the region of best hearing compared to other frequencies. Furthermore, animals showed behavioral signs of tinnitus during that time window and frequency range as assessed by gap prepulse inhibition of the acoustic startle reflex (GPIAS). In contrast to animals with noise trauma-induced tinnitus, salicylate-induced tinnitus animals showed no correlation between hearing thresholds and behavioral signs of tinnitus, indicating that the development of tinnitus after salicylate injection is not based on SR as proposed for the trauma model. In other words, salicylate-induced tinnitus and noise trauma-induced tinnitus are not based on the same neurophysiological mechanism.

Preventive Effects of Ginkgo-Extract EGb 761® on Noise Trauma-Induced Cochlear Synaptopathy

“…We always combine the results of the GPIAS paradigm with physiological results such as hearing loss, which should be—according to our hypothesis—correlated with the strength of the tinnitus, i.e., the effect size. In a recent publication, we were able to show exactly this correlation [ 31 ], supporting the validity of the method. In line with our animal-experiment tested hypothesis [ 8 , 9 , 20 , 22 , 49 , 50 ], as well as with human patient studies and treatment approaches [ 18 , 19 , 51 ], these animals, therefore, do show behavioral signs of tinnitus.…”

“…The experimenters were blinded to the content of the medium applied (control or EGb 761 ® ). All methods used have been described elsewhere [ 20 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ] and are, therefore, only briefly described below and schematically depicted in Figure 1 . Briefly, agar medium was applied orally by 15 daily applications, either 3 weeks before or after a mild monaural acoustic noise trauma.…”

Behavioral assessment of Zwicker tone percepts in rodents

“…the 5 kHz percept is easier to detect compared to a 2 kHz percept. Additionally, it has already been shown that a GPIAS paradigm is at least partially dependent on cortical learning mechanisms (Moreno-Paublete et al ., 2017; Lanaia et al ., 2021), which may interact (e.g. suppress) the percept after consecutive presentation.…”

MicroRNA-375-3p Alleviates Salicylate-Induced Neuronal Injury by Targeting ELAVL4 in Tinnitus

“…4 There is currently no cure for tinnitus, which is greatly related to the poor understanding of the mechanism underlying tinnitus onset. 5 Salicylate-induced tinnitus model has been widely used for investigating the biological mechanism underlying tinnitus. High doses of salicylate can enhance auditory thresholds, decrease otoacoustic emissions, and reliably trigger tinnitus.…”