Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus. Here, we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells (IHCs). We found that IHCs showed significant damage after exposure to a high concentration of salicylate. Whole-cell patch clamp recordings showed that 1-5 mmol/L salicylate did not affect the exocytosis of IHCs, indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input. Instead, salicylate induced a larger peak amplitude, a more negative half-activation voltage, and a steeper slope factor of Ca²⁺ current. Using noise analysis of Ca²⁺ tail currents and qRT-PCR, we further found that salicylate increased the number of Ca²⁺ channels along with Ca_V1.3 expression. All these changes could act synergistically to enhance the Ca²⁺ influx into IHCs. Inhibition of intracellular Ca²⁺ overload significantly attenuated IHC death after 10 mmol/L salicylate treatment. These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.
Animals ; Calcium ; Exocytosis ; Hair Cells, Auditory, Inner ; Mice ; Sodium Salicylate/pharmacology* ; Tinnitus/chemically induced*

This study aims to investigate corticofugal modulation on spontaneous activities of the external nucleus of the inferior colliculus (ICx) in a salicylate acid (SA) induced tinnitus rat model by the stimulation of the primary auditory cortex (AI). Extracellular recording techniques and stereotaxic method were used. The spontaneous activities of a single unit were recorded from the left ICx after electrical stimulation was given to the left AI of the rats duplicated as acute SA models. The average rate of spontaneous discharge and the interspike interval histogram of spontaneous activities were used as indices. The single unit spontaneous discharges of the same unit of ICx before and after AI stimulation were observed. There was an inhibitory effect of AI stimulation on the activities of the high discharge unit [(8.75+/-2.70) Hz vs (5.06+/-2.01) Hz] and a facilitatory effect on the low discharge unit [(1.41+/-0.45) Hz vs (2.46+/-0.79) Hz]. In the normal group, there was a restraining effect on the average rate of spontaneous discharge of the ICx after AI stimulation. The average rate of spontaneous discharge changed from (3.66+/-0.84) Hz to (2.47+/-0.43) Hz in the first hour after AI stimulation and then recovered within 2-4 h. And the discharge rate of the spike interval within 0-20 ms decreased (17% vs 7.3%, 11.2%) in the first 2 h and recovered 3-4 h after AI stimulation. The discharge rate of the spike interval within 0-6 ms (short interval) recovered 2 h after AI stimulation. In the acute SA model group, the average rate of spontaneous discharge recorded from the ICx decreased from (7.48+/-0.85) Hz to (3.38+/-0.39) Hz in the first hour after AI stimulation and the suppression effect remained 4 h (P<0.05). There was no difference in the average rate of spontaneous discharge between the acute SA model group and the normal group at 2-4 h after AI stimulation. The suppression effect after AI stimulation on the 0-20 ms interval spikes in the ICx lasted 4 h, while that on the shorter interval (0-6 ms) spikes recovered in the 3rd hour after AI stimulation in acute SA model group. It is concluded that the high average spontaneous discharge rate of ICx in acute SA model decreases significantly by AI stimulation, and the suppression effects on the shorter interval spikes recovers in the 3rd hour after AI stimulation. It might be inferred that stimulation of AI, through exciting the auditory descending projections, could remit the increased spontaneous discharge of ICx induced by SA that may relate with tinnitus in a period of time.
Animals ; Auditory Cortex ; physiopathology ; Disease Models, Animal ; Electric Stimulation ; Inferior Colliculi ; physiopathology ; Rats ; Salicylates ; adverse effects ; Tinnitus ; chemically induced ; physiopathology

In this article, current status of noise exposure in workplaces, trend of workers with noise-induced hearing loss (NIHL), and prevalence of NIHL in workers by industry and job category in Korea were reviewed. In addition, trends of research on the audiological effects such as hearing loss from noise and occupational hearing loss from non-noise in Korea were addressed through reports in industrial audiology. Though noise exposure level has improved, noise still shows the highest rate of cases exceeding exposure limit among workplace hazards. NIHL is the most common occupational disease except work-related disease such as musculoskeletal disorders and cerebrovascular diseases, and NIHL prevalence is thought to be much higher than reported in official publications. Noise affecting hearing comes from various sources such as workplaces, military settings, areas with exposure to high noise, and specific noise sources. There is also occupational hearing loss by non-noise including chemicals such as organic solvents and heavy metals, barotrauma, and trauma due to welding spark. Noise affects daily life through audiological effects such as hearing loss and tinnitus, non-audiological physical effects (e.g., cardiovascular), and psychosocial and behavioral effects. Development of systematic and comprehensive hearing conservation programs for lowering the noise level in workplaces and preventing the NIHL, and preparation of technological, administrative system for its settlement at workplace are urgently needed.
Hearing Loss/*chemically induced ; Hearing Loss, Noise-Induced/*epidemiology ; Humans ; Noise, Occupational/*adverse effects ; Occupational Diseases/chemically induced/*epidemiology/*etiology ; Occupational Exposure/adverse effects ; Prevalence ; Republic of Korea/epidemiology ; Tinnitus/epidemiology

OBJECTIVE: To observe the expression of corticotropin-releasing factor-1 receptor in hippocampus of rats model of salicylate induced tinnitus. METHOD: Twenty-four rats were randomly divided into three groups, eight for each group. For Group A and Group B, 10% salicylic sodium solution was intraperitoneal injected each day at the dose of 350 mg/kg for 21 days in Group A and 14 days in Group B. Group C received intraperitoneal injection with the same amount of saline solution each day for 14 days. ABR were tested 2 days before, and 2 hours after the first administration and after the last injection. Immunohistochemical test and Western Blot were utilized to detect the expression of CRF1R in hippocampus for each group. RESULT: ABR thresholds tested 2 days before the first administration of the 3 groups showed no statistically significant difference (P > 0.05). At the time point of 2 hours after the first injection, the ABR thresholds of Group A and Group B rose by 25.90 dB SPL and 25.03 dB SPL compared with that before the administration, respectively (P < 0. 01). After the last administration, the ABR thresholds of Group A and Group B rose 34.91 dB SPL and 32.62 dB SPI. compared with that before the administration, respectively (P < 0.01). The ABR thresholds of Group C showed no significant statistical difference at all the tested time points (P > 0.05). Immunohistochemical test and Western Blot revealed that the expression level of CRF1R in the hippocampus was A > B > C (P < 0.05). CONCLUSION The expression of CRF1R in the hippocampus of salicylate induced tinnitus rat increased with the injection time, illustrating that CRF1R may participate in the mechanism of tinnitus involving the limbic system.
Animals ; Auditory Threshold ; Disease Models, Animal ; Hippocampus ; metabolism ; Injections, Intraperitoneal ; Rats ; Receptors, Corticotropin-Releasing Hormone ; metabolism ; Salicylates ; adverse effects ; Tinnitus ; chemically induced ; metabolism

AIMObserve the effects of er-long-zuo-ci-wan (EIZCW, a compound of Chinese Traditional Medicine) on the spontaneous discharge of external cortex of inferior colliculus (ICx) and secondary auditory cortex (AII) of chronic tinnitus model rats induced by salicylate acid, to explore the neural mechanisms underlying ELZCW preventing tinnitus.

METHODS30 adult SD rats were involved and divided into three groups, normal control group, chronic tinnitus model group and ELZCW prevention group. Extracellular recording techniques and stereotaxic method were used. The spontaneous spikes were recorded and analyzed from ICx and all in different group rats. The average rate of spontaneous discharge and the interspike interval histogram of spontaneous activities were used as indexes.

RESULTS(1) Compared with normal control group, the average rate of spontaneous discharge recorded from the ICx in the chronic tinnitus model group increased significantly (4.57 +/- 0.54 Hz vs. 3.14 +/- 0.40 Hz, P < 0.05). Furthermore analysis showed that the discharge rate of short spike interval from the ICx in the chronic tinnitus model group increased than that of the normal group (0-40 ms: 58% vs. 40%; 0-4 ms: 9% vs. 5%). And there was an increasing tendency of the average rate of spontaneous discharge recorded from the AII in the chronic tinnitus model group compared with that in the normal group. (2) Compared with the chronic tinnitus model group, the average rate of spontaneous discharge recorded from the ICx and AII in the ELZCW prevention group significantly decreased than that in the chronic tinnitus model group (ICx: 2.41 +/- 0.21 Hz vs. 4.57 +/- 0.54 Hz, P < 0.01. AII: 2.24 +/- 0.24 Hz vs. 4.57 +/- 0.54 Hz , P < 0.01). And the discharge rate of short spike interval from the ICx and AII in the chronic tinnitus model group decreased than that in the normal control group (ICx: 0-40 ms 50% vs. 58%, 0-4 ms 4% vs. 9%. All: 0-22 ms: 24% vs. 31%, 0-8 ms 19% vs. 16%).

CONCLUSIONIf the increasing of the spontaneous activities of ICx and AII in chronic tinnitus rats means tinnitus, the use of ELZCW could decrease this kind of changes.

Animals ; Auditory Cortex ; physiopathology ; Auditory Pathways ; drug effects ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Male ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Salicylic Acid ; Tinnitus ; chemically induced ; drug therapy ; physiopathology