jueves, 4 de octubre de 2012

Isoflurane blocks temporary tinnitus

Research paper
AUTHORS
  • Institute of Neuroscience, Department of Psychology, 1254 University of Oregon, Eugene, OR 97403, USA

Abstract

Temporary tinnitus is a common consequence of noise exposure, and may share important mechanisms with chronic tinnitus

Noise-induced hearing loss is the most prevalent cause of chronic tinnitus

The reversibility of temporary tinnitus offers some practical experimental advantages. 

We therefore adapted a behavioral method based on gap detection to measure temporary tinnitus following brief acoustic trauma. 



Although anesthesia is often used during acoustic trauma exposure, many anesthetics can protect against noise-induced hearing loss.



Whether anesthesia during acoustic trauma affects temporary tinnitus therefore remains an open question that directly affects experimental design in tinnitus studies. 

Here we tested whether anesthetizing rats with isoflurane during trauma had any effect on tinnitus

We found that gap-detection deficits, a behavioral measure of tinnitus, were 5 times stronger and lasted 10 times longer when isoflurane was not used. 

This suggests that isoflurane largely prevents temporary noise-induced tinnitus.

Highlights

► We used a behavioral gap-detection method to measure temporary tinnitus in rats following brief acoustic trauma. 
► We tested whether anesthetizing rats with isoflurane during trauma had any effect on on tinnitus
► We found that tinnitus was 5 times stronger and lasted 10 times longer when isoflurane was not used. 
► These results suggest that isoflurane largely prevents temporary noise-induced tinnitus.

Figures and tables from this article:
Full-size image (35 K)
Fig. 1. Gap detection measure of temporary tinnitus. a) Example of startle responses (arrows) of an animal to a white noise burst embedded in background narrow-band noise. Top panel shows the startle response to the noise burst presented in isolation (black lines: 20 individual trials; red line: mean across trials; grey line: stimulus). Stimulus is clipped. Bottom panel shows that the startle response is reduced when the white noise burst is preceded by a 50 ms gap in the background noise. Startle response amplitude is in arbitrary units. b) Peak startle response amplitudes for the raw data shown in (a). Black circles: 20 individual trials; grey dots: mean across trials; *indicates that the gap caused a significant decrease in peak startle amplitude (p < 10−2). The decreased startle response demonstrates successful gap detection by the animal, with a tinnitus index (see Methods) of 0.0002 (i.e., no tinnitus). c) Schematic of time course for a typical experiment (G: gap detection task, N: noise detection task. Blocks of tasks were repeated (indicated by…) until performance returned to baseline. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Full-size image (77 K)
Fig. 2. Isoflurane blocks temporary tinnitus. a) Time course of temporary tinnitus following brief noise trauma. Animals (n = 10) were not anesthetized with isoflurane during pure-tone trauma. Note that tinnitus index rose sharply after trauma and remained elevated for hours. Symbols in a, b, e, f indicate different animals. b) Time course of tinnitus when animals were anesthetized with isoflurane during noise trauma. These are the same 10 animals as in (a), but tested at least 2 days apart. c) The maximum tinnitus index was significantly greater when isoflurane was not used (p < 10−2). d) Tinnitus duration was significantly longer when isoflurane was not used (p < 0.05). Tinnitus duration was defined as the amount of time that the tinnitus index exceeded 0.05. e) A reduction in %GPIAS (consistent with presence of tinnitus) showed a similar time course as the increase in tinnitus index in (a) for animals not anesthetized with isoflurane during trauma. f) Animals anesthetized during trauma showed no reduction in %GPIAS. g) The maximal change in %GPIAS from baseline was significantly greater when isoflurane was not used (p < 10−2). Error bars in c, d, g indicate standard errors of the mean.
Full-size image (48 K)
Fig. 3. Narrow band noise detection thresholds. a) Example of startle responses of an animal to a white noise burst without any background noise. In the top panel, the white noise burst is presented in isolation. In the lower panels, the burst is preceded by a narrow-band prepulse, with the prepulse level indicated at left (prepulse bandwidth was ⅓ octave and center frequency was 6 kHz). Note that the startle response was progressively reduced as the prepulse level was increased. Startle response amplitude is in arbitrary units. b) Peak startle response amplitudes for the raw data shown in (a). Black circles: 20 individual trials; grey filled circles: mean across trials; *indicates that the prepulse caused a significant (p < 0.05) decrease in peak startle amplitude. We used the lowest prepulse level that significantly reduced startle as an estimate (upper bound) of detection threshold (50 dB in this example). c) Time course of detection threshold, expressed as dB relative to the background noise level used in the gap detection task. Detection threshold averaged −19 ± 6 dB and never exceeded −5 dB, indicating that animals could always hear the background noise used in the gap detection task.
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